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ABSTRACTUrban lakes and ponds (L&Ps) provide numerous ecological and social services for local populations living in urban areas. Their monitoring and management are mostly based on water quality and ecological indicators and poorly consider public preferences and expectancies related to these artificial ecosystems. Even fewer studies bring together expert indicators and public expectations to inform management objectives for urban lakes. Based on an interdisciplinary study, this paper compares an expert assessment of the ecological quality of three urban L&Ps located in the Ile-de-France area with the public perception of these lakes. This approach permits us to explore the compatibilities and incongruences between the various ways in which scientists, managers and urban users assess urban L&P quality. Based on these data, we discuss how it could be possible to define management objectives that integrate quality indicators and expect these objectives to be used in a territorial approach that might allow to obtain a better adequacy between social users’ expectations and the ecological status of these L&Ps.

An intercomparison of four regional air quality models is performed in the tropical megacity of São Paulo with the perspective of developing a forecasting system based on a model ensemble. Modeled concentrations of the main regulated pollutants are compared with combined observations in the megacity center, after analyzing the spatial scale of representativeness of air monitoring stations. During three contrasting periods characterized by different types of pollution events, the hourly concentrations of carbon monoxide (CO), nitrogen oxides (NOx), sulfur dioxide (SO2), and particulate matter (PM2.5and PM10) modeled by the ensemble are in moderate agreement with observations. The median of the ensemble provides the best performance (R≈ 0.7 for CO, 0.7 for NOx, 0.5 for SO2, 0.5 for PM2.5, and 0.4 for PM10) because each model has periods and pollutants for which it has the best agreement. NOx concentration is modeled with a large inter‐model variability, highlighting potential for improvement of anthropogenic emissions. Pollutants transported by biomass burning events strongly affect the air quality in São Paulo and are associated with significant inter‐model variability. Modeled hourly concentration of ozone (O3) is overestimated during the day (≈20 ppb) and underestimated at night (≈10 ppb), while nitrogen dioxide (NO2) is overestimated at night (≈20 ppb). The observed O3concentration is best reproduced by the median of the ensemble (R≈ 0.8), taking advantage of the variable performance of the models. Therefore, an operational air quality forecast system based on a regional model ensemble is promising for São Paulo. Forecasting air quality in megacities is particularly difficult due to the diversity and temporal variability of emission sources. São Paulo is the largest metropolitan area in South America and has no operational air quality forecast. We perform an intercomparison of four regional air quality models with the perspective of developing an air quality forecasting system. During three contrasting periods characterized by different types of pollution events, we analyze the modeled concentrations of the main regulated pollutants (trace gases and aerosols) compared to observations from the São Paulo air quality monitoring network. The modeled concentrations of the main regulated pollutants agree well with the observations range of variation, although we show the potential in improving the treatment of anthropogenic emissions. In addition, the long‐range transport of pollutants due to forest fires strongly affects the air quality in São Paulo and also reduces the performance of the models. The observed hourly ozone concentration is well reproduced by the models, and its median has the best performance, taking advantage of the capabilities of each model. Therefore, an operational air quality forecasting system for the megacity of São Paulo is promising. An ensemble of regional air quality models performs well in the São Paulo megacity for the main regulated pollutants (CO, NOx, O3, SO2, PM2.5, and PM10)Transport of pollutants due to biomass burning events, affecting strongly the air quality of the megacity, is represented with high variability by the ensembleIn the center of the megacity, the median of the regional model ensemble leads to the best performance for these pollutants compared to each model that composes it An ensemble of regional air quality models performs well in the São Paulo megacity for the main regulated pollutants (CO, NOx, O3, SO2, PM2.5, and PM10) Transport of pollutants due to biomass burning events, affecting strongly the air quality of the megacity, is represented with high variability by the ensemble In the center of the megacity, the median of the regional model ensemble leads to the best performance for these pollutants compared to each model that composes it

Total and wet mineral dust deposition has been monitored since 2006 at three Sahelian stations in Senegal, Mali, and Niger, respectively at the weekly and the event time scale. Average annual deposited mass fluxes range from 75 to 183?g?m-2?yr-1, from west to east. Deposition fluxes exhibit a clear seasonal cycle in Mali and Niger. High wet deposition fluxes result from an optimum phasing between dust concentration and precipitation: the maximum occurring at the beginning of the wet season, after the maximum of dust concentration and before the precipitation maximum. The contribution of wet to total deposition varies from 67% in Mali to 8% in Senegal. It is the main factor of variability of the deposition fluxes from year to year and at the seasonal scale in Niger and Mali. Wet deposition fluxes in Mali and Niger are mainly due to the wash out of dust emitted by convective systems. In Senegal, the deposition fluxes are lower and dominated by dry deposition (92% of the annual deposition flux). This is due to the low occurrence of convective systems producing local dust emissions and intense wet deposition. The dry deposition fluxes are primarily driven by the variability of the dust concentration. The dry deposition velocities derived from our measurements are consistent with those estimated by theoretical models. Scavenging ratios computed from the measured wet deposition fluxes, dust concentrations, and precipitation are anticorrelated with precipitation amounts. This suggests that most of the atmospheric dust is scavenged at the very beginning of the precipitation events. Annual deposition is of the order of 100?g?m-2Wet deposition is the main source of variabilityDry deposition is primarily controlled by dust concentration

L’hydrologie urbaine, en tant que discipline scientifique à vocation appliquée, s’est progressivement développée en France à travers des réseaux qui associent professionnels des services d’assainissement des collectivités locales et scientifiques des laboratoires de recherche. Les observatoires d’hydrologie urbaine (OPUR en région parisienne, l’OTHU à Lyon, et l’Onevu à Nantes) sont la dernière étape de ce processus d’institutionnalisation. L’article montre comment ces nouveaux acteurs collectifs influencent le processus d’innovation dans la gestion des eaux pluviales : ils transforment les logiques d’action des services urbains de ces métropoles, en insufflant une culture du suivi et de l’évaluation appuyée sur une « rationalité analytique ». Un peu en marge de ce réseaux scientifiques et techniques, des collectivités de taille plus modeste (Rennes et le Douaisis) révèlent d’autres modes de production de l’innovation, privilégiant une approche « fonctionnelle et pragmatique » et la mise en place de solutions locales. Nous montrons ainsi comment Rennes et le Douaisis donnent à voir une innovation assez radicale, qui se passe a prioride (pré)caution scientifique, alors que le modèle des métropoles adossées aux observatoires favorise une innovation plus précautionneuse.La réalité est cependant plus nuancée : l’expertise produite par OPUR, l’OTHU et l’Onevu est diffusée bien au-delà de leur propre réseau, rendant de fait la prise de risques des collectivités « sans observatoires » plus limitée.

En France, depuis 2011, les collectivités peuvent instaurer une taxe pour la gestion des eaux pluviales urbaines. Cette taxe est susceptible de leur permettre, d’une part, d’inciter à une maîtrise à la source de l’imperméabilisation et des débits d’eaux pluviales et, d’autre part, de dégager des ressources pour répondre aux difficultés de financement de cette gestion. Sa saisie constitue a prioriun cap dans la construction d’un service public de gestion des eaux pluviales. C’est également un moment privilégié pour questionner cette gestion à partir des finances publiques en termes de choix politiques, de contraintes financières et de capacité d’action. Aussi, une démarche a été engagée pour observer et analyser les conditions de saisie de ce nouvel instrument. Quelques collectivités ont déjà délibéré pour l’instaurer, un certain nombre étudient l’opportunité de le faire. Après une présentation de la construction de cette taxe en France, un premier panorama des conditions d’appro priation par les collectivités est dressé. Il permet d’appréhender ce que la fiscalité nous révèle de l’action publique en matière de gestion des eaux pluviales aujourd’hui.

Germinal centers (GCs) are sites of B-cell clonal expansion, hypermutation, and selection. GCs are polarized into dark (DZ) and light zones (LZ), a distinction that is of key importance to GC selection. However, the difference between the B cells in each of these zones in humans remains unclear. We show that, as in mice, CXCR4 and CD83 can be used to distinguish human LZ and DZ cells. Using these markers, we show that LZ and DZ cells in mice and humans differ only in the expression of characteristic “activation” and “proliferation” programs, suggesting that these populations represent alternating states of a single-cell type rather than distinct differentiation stages. In addition, LZ/DZ transcriptional profiling shows that, with the exception of “molecular” Burkitt lymphomas, nearly all human B-cell malignancies closely resemble LZ cells, which has important implications for our understanding of the molecular programs of lymphomagenesis.

Germinal centers (GCs) are sites of B-cell clonal expansion, hypermutation, and selection. GCs are polarized into dark (DZ) and light zones (LZ), a distinction that is of key importance to GC selection. However, the difference between the B cells in each of these zones in humans remains unclear. We show that, as in mice, CXCR4 and CD83 can be used to distinguish human LZ and DZ cells. Using these markers, we show that LZ and DZ cells in mice and humans differ only in the expression of characteristic “activation” and “proliferation” programs, suggesting that these populations represent alternating states of a single-cell type rather than distinct differentiation stages. In addition, LZ/DZ transcriptional profiling shows that, with the exception of “molecular” Burkitt lymphomas, nearly all human B-cell malignancies closely resemble LZ cells, which has important implications for our understanding of the molecular programs of lymphomagenesis.

Energy system models underpin decisions by energy system planners and operators. Energy system modeling faces a transformation: accounting for changing meteorological conditions imposed by climate change. To enable that transformation, a community of practice in energy-climate modeling has started to form that aims to better integrate energy system models with weather and climate models. Here, we evaluate the disconnects between the energy system and climate modeling communities, then lay out a research agenda to bridge those disconnects. In the near-term, we propose interdisciplinary activities for expediting uptake of future climate data in energy system modeling. In the long-term, we propose a transdisciplinary approach to enable development of (1) energy-system-tailored climate datasets for historical and future meteorological conditions and (2) energy system models that can effectively leverage those datasets. This agenda increases the odds of meeting ambitious climate mitigation goals by systematically capturing and mitigating climate risk in energy sector decision-making.

Using the CAM‐chem Model, we simulate the response of chemical species in the free troposphere to scenarios of primary pollutant emission reductions during the COVID‐19 pandemic. Zonally averaged ozone in the free troposphere during Northern Hemisphere spring and summer is found to be 5%–15% lower than 19‐yr climatological values, in good agreement with observations. About one third of this anomaly is attributed to the reduction scenario of air traffic during the pandemic, another third to the reduction scenario of surface emissions, the remainder to 2020 meteorological conditions, including the exceptional springtime Arctic stratospheric ozone depletion. For the combined emission reductions, the overall COVID‐19 reduction in northern hemisphere tropospheric ozone in June is less than 5 ppb below 400 hPa, but reaches 8 ppb at 250 hPa. In the Southern Hemisphere, COVID‐19 related ozone reductions by 4%–6% were masked by comparable ozone increases due to other changes in 2020. The reduction in the emissions of primary air pollutants during the 2020 COVID‐19 pandemic has generated perturbations in the chemical state of the atmosphere. A global Earth system model that accounts for chemical, physical, and dynamical processes in the atmosphere and for the coupling between the atmosphere, the ocean and the land surface, indicates that the abundance of tropospheric ozone was significantly reduced during the pandemic in response to realistic scenarios of reduced emissions of primary pollutants associated with restrictions of air traffic and economic activities. These simulated findings are consistent with observed ozone anomalies during the summer of 2020. The ozone concentration in the northern extratropical free troposphere was 5%–15% lower in May and June 2020 relative to climatologyA third of this anomaly is attributed to meteorological conditions including stratospheric Arctic air with abnormally low ozoneThe assumed reduction in surface and aircraft emissions associated with the COVID‐19 pandemic can explain an ozone anomaly of 4%–8% The ozone concentration in the northern extratropical free troposphere was 5%–15% lower in May and June 2020 relative to climatology A third of this anomaly is attributed to meteorological conditions including stratospheric Arctic air with abnormally low ozone The assumed reduction in surface and aircraft emissions associated with the COVID‐19 pandemic can explain an ozone anomaly of 4%–8%

Abstract: The aim of our study was to determine the main ionic mechanisms responsible for the electrophysiological alterations of ventricular action potentials associated with cardiac dilation in a strain of cardiomyopathic Syrian hamsters which does not develop hypertrophy during the first five months of life. Right and left ventricular action potentials (APs) were recorded in Langendorff perfused isolated hearts from dilated cardiomyopathic (MS 200) and normal hamsters at 60, 120, and 180 days of age. AP characteristics differed in the two ventricles and in different regions (base, apex) of the left ventricle in both strains. When recorded in a given region (apex), the plateau was always of higher amplitude and longer duration, i.e., of larger area, in diseased as compared in normal hearts. The participation of the calcium-independent 4-aminopyridine (4-AP) sensitive transient outward current, Ito1, in the left ventricular AP plateau repolarization was smaller in dilated than in control hearts at any age and AP area was the same in both strains at 60 days of age in the presence of 4-AP. The participation of the cadmium (Cd) sensitive L-type Ca current was investigated in the development of AP plateau at 120 days of age and was smaller in dilated than in control hearts. The participation of the Na-Ca exchange inward current, INa-Ca, in the development of the AP plateau was similar in both strains at 60 days of age; later on, it strongly decreased in control hearts, whereas it remained high in diseased hearts. The tetrodotoxin sensitive slowly inactivating inward current was not increased in dilated hearts compared to control hearts. Our results show that the AP lengthening observed, in dilated non-hypertrophic hamster hearts, results essentially from a reduced participation of Ito1 at 60 days of age, whereas it results from both a reduced participation of Ito1 and an increased participation of INa-Ca at 120 and 180 days of age.

The effect of 10 nM atrial natriuretic peptide (ANF) on macroscopic L-type calcium current, ICa, and calcium-independent outward potassium current, Ilo, were studied in myocytes isolated from human atrial trabeculae using the whole-cell-recording patch-clamp technique. When cells were dialysed with pipette media containing 0.2 mM GTP, ANF reduced ICa by 37.81%±5.4% at +20mV and Ilo by 21.72%±3.68% at +60 mV in a reversible manner. When ICa was increased by ß-adrenoreceptor stimulation (0.1 µM isoproterenol) or by the phosphodiesterase inhibitor isobutylmethylxanthine (10 µM) ANF reduced ICa by 24.99±3.4% and by 39.9±6.3% respectively. In cells dialysed with GTP-free pipette media, ANF increased ICa markedly (39.8%±7%) and reversibly, whereas it still depressed Ilo (18.92%±2%). Addition of 0.2 mM GTP[?S] to the pipette solution in the absence of GTP increased ICa, decreased Ilo and suppressed the effect of ANF on both ICa and Ilo. It is suggested that activation of the ANF receptor in human atrial cells reduces ICa via guanylate-cyclase-dependent cGMP production, increases ICa via Gs protein activation and decreases Ilo via Gi protein activation.

CHF1194 is an inclusion complex of ß-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, ß-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-ß-cyclodextrin is wettable and more water soluble, the absorption rate of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged.

The effects of sodium palmitate were studied on the transmem-brane potential properties of canine subendocardial Purkinje fibers and on the Purkinje fibers of the dog and the sheep false tendons with standard microelectrode technique. Following 4 h of superfusion with palmitate/albumin = 10, action potential duration in all preparations was prolonged (p < 0.05), and resting membrane potential, action potential amplitude, and maximum rate of rise were slightly but significantly (p < 0.05) diminished in the subendocardial preparation, but not in the false tendons. Action potential prolongation was reversible in the dog preparations but only partially reversible in the sheep Purkinje fibers. Following palmitate-induced prolongation of the action potential duration, rapid spontaneous diastolic depolarization was observed in the subendocardial Purkinje fibers. Palmitale enhanced spontaneous diastolic depolarization in the sheep but not in the dog Purkinje fibers (false tendons). Albumin alone had no effect on all action potential properties in both species. It is concluded that extended periods of exposure of the ventricular specialized conducting tissue to excess levels of palmitate can induce action potential abnormalities and subsequent rhythm disturbances both in the dog and the sheep.

We determined whether the dilated cardiomyopathy which develops between 30 and 140 days of age in the Syrian hamster strain MS200, before the onset of cardiac hypertrophy and failure, is associated with alterations in both the action potential (AP) and the Ca2 +-independent transient outward current, Ito1. AP was recorded in perfused hearts using microelectrodes and Ito1was recorded in single ventricular myocytes using the whole-cell patch-clamp. The MS200 strain was compared to the control CHF148 strain at different periods of age (60, 90, 120 and 180 days). APs were markedly lengthened in MS200 compared to CHF148 hearts at all ages studied. Cell membrane capacitance increased with age in the two strains, but was not significantly higher in MS200 than in CHF148 of a given age, indicating the absence of cell hypertrophy. At 60 days of age, Ito1density was the same in the two strains. Later on, Ito1density increased markedly at 90 –120 days then decreased at 180 days in CHF148, whereas this increase was delayed and of reduced amplitude in MS200. The sustained component of outward current, Isus, was not sizeably different in the two strains. The conductance –voltage and steady-state inactivation relationships were shifted with age towards positive potentials by 15 mV in the two strains, but earlier in MS200 (90 days) than in CHF148 (180 days). Similarly, the recovery of Ito1from inactivation exhibited a slow component which increased with age in the two strains but was larger in MS200 than in CHF148. In conclusion, alterations of Ito1may contribute to changes in shape of AP, but cannot entirely explain dilation-induced AP lengthening.

Quinidine and flecainide, two class-I antiarrhythmics increase action potential duration (APD) at 90% repolarization and cellular refractory period in human atrial fibers without significant change in resting potential. On the other hand, quinidine decreases APD at 50%, whereas flecainide slightly increases, which suggests different effects on Ca2+ current. Using isolation cell procedure and whole cell recording, we found that 10 µM quinidine (34.77±6.5%, n=5) and 0.5 µM flecainide (50.46±6.2%, n=4) decrease calcium current in human atrium. It is concluded that, at therapeutical concentrations, quinidine and flecainide modify the action potential plateau phase in a different manner, which is not only related to the calcium current decrease.

We use the global Community Earth System Model to investigate the response of secondary pollutants (ozone O3, secondary organic aerosols SOA) in different parts of the world in response to modified emissions of primary pollutants during the COVID‐19 pandemic. We quantify the respective effects of the reductions in NOx and in volatile organic carbon (VOC) emissions, which, in most cases, affect oxidants in opposite ways. Using model simulations, we show that the level of NOx has been reduced by typically 40% in China during February 2020 and by similar amounts in many areas of Europe and North America in mid‐March to mid‐April 2020, in good agreement with space and surface observations. We show that, relative to a situation in which the emission reductions are ignored and despite the calculated increase in hydroxyl and peroxy radicals, the ozone concentration increased only in a few NOx‐saturated regions (northern China, northern Europe, and the US) during the winter months of the pandemic when the titration of this molecule by NOx was reduced. In other regions, where ozone is NOx‐controlled, the concentration of ozone decreased. SOA concentrations decrease in response to the concurrent reduction in the NOx and VOC emissions. The model also shows that atmospheric meteorological anomalies produced substantial variations in the concentrations of chemical species during the pandemic. In Europe, for example, a large fraction of the ozone increase in February 2020 was associated with meteorological anomalies, while in the North China Plain, enhanced ozone concentrations resulted primarily from reduced emissions of primary pollutants. With the reduction in economic activities following the COVID‐19 pandemic outbreak in early 2020, most emissions of air pollutants (i.e., nitrogen oxides [NOx], carbon monoxide [CO], sulfur dioxide [SO2], volatile organic carbon [VOC], black carbon [BC], organic carbon [OC]) have decreased substantially during several months in different regions of the world. This unintended global experiment offered a glimpse into a potential future in which air quality would be improved. Here, a global atmospheric model is used to assess the changes in the chemical composition of the atmosphere during the pandemic period and in the related chemical processes that lead to the formation of ozone (O3) and secondary organic aerosols (SOA). The study illustrates the nonlinearity of the air quality response to reduced NOx and VOC emissions, which depends on the chemical environment including the background level of nitrogen oxides. Meteorological variability can lead to anomalies in the concentration of chemical species with magnitudes that are as large or even larger than the perturbations due to COVID‐induced changes in the emissions. During the COVID‐19 lockdown, the atmospheric concentration of primary pollutants (NOx, VOCs, CO, SO2) was considerably reducedThe concentration of secondary pollutants increased in NOx‐saturated areas and decreased in NOx‐limited areasThe response of the chemical system depends on the relative changes in NOx and VOC emissions, and is affected by weather variability During the COVID‐19 lockdown, the atmospheric concentration of primary pollutants (NOx, VOCs, CO, SO2) was considerably reduced The concentration of secondary pollutants increased in NOx‐saturated areas and decreased in NOx‐limited areas The response of the chemical system depends on the relative changes in NOx and VOC emissions, and is affected by weather variability

Bacterial meningitis is an ongoing threat for the population of the African Meningitis Belt, a region characterized by the highest incidence rates worldwide. The determinants of the disease dynamics are still poorly understood; nevertheless, it is often advocated that climate and mineral dust have a large impact. Over the last decade, several studies have investigated this relationship at a large scale. In this analysis, we scaled down to the district-level weekly scale (which is used for in-year response to emerging epidemics), and used wavelet and phase analysis methods to define and compare the time-varying periodicities of meningitis, climate and dust in Niger. We mostly focused on detecting time-lags between the signals that were consistent across districts. Results highlighted the special case of dust in comparison to wind, humidity or temperature: a strong similarity between districts is noticed in the evolution of the time-lags between the seasonal component of dust and meningitis. This result, together with the assumption of dust damaging the pharyngeal mucosa and easing bacterial invasion, reinforces our confidence in dust forcing on meningitis seasonality. Dust data should now be integrated in epidemiological and forecasting models to make them more realistic and usable in a public health perspective.

<$O_ST_ABS>Objective<$C_ST_ABS>The aim of our study was to determine the main electrophysiological alterations associated with cardiac dilation in MS200 strain Syrian hamsters, a model of genetically determined cardiomyopathy. <$O_ST_ABS>Methods<$C_ST_ABS>Ventricular action potentials (APs) were recorded with standard microelectrodes in isolated hearts from 120-day-old cardiomyopathic (strain MS200) and age-matched control (strain CHF148) Syrian hamsters. Ionic currents were recorded from single ventricular myocytes using the whole-cell patch-clamp technique. <$O_ST_ABS>Results<$C_ST_ABS>In MS200, AP was prolonged and the plateau phase was markedly increased as compared to CHF148. Differences in both AP duration and 4-aminopyridine-induced AP lengthening between epicardial and endocardial tissues were less marked in MS200 than in CHF148 ventricles. Cell size and membrane capacitance were not higher in MS200 than in CHF148 myocytes, indicating the absence of cell hypertrophy in myopathic ventricles. The L-type calcium current (I_Ca,L) density was significantly reduced in MS200 and the voltage-dependence of both steady-state activation and inactivation was altered. The voltage-dependent outward current was composed of both transient (I_to1) and sustained (I_ss) components, respectively sensitive and insensitive to 4-aminopyridine. I_to1 density was strongly depressed in MS200 compared to CHF148, whereas I_ss density was only slightly reduced. The conductance-voltage and steady-state inactivation relationships for I_to1 were shifted to more positive potentials in MS200. The I_to1 recovery process was markedly slower in MS200 than in CHF148. The steady-state current-voltage relationships, in the physiological voltage range, were superimposable in MS200 and CHF148. <$O_ST_ABS>Conclusions<$C_ST_ABS>In ventricular myocytes from dilated heart of MS200 Syrian hamsters, I_to1 is more drastically depressed than I_Ca,L. Such an observation might partially explain dilation-induced AP lengthening.

The electrophysiological effects of three class I antiarrhythmic drugs, lignocaine, disopyramide, and penticainide, were compared in sheep cardiac Purkinje fibres. Action potential duration was shortened with all three drugs, the effect being small with disopyramide, moderate with penticainide, and greatest with lignocaine. Slowing down of the early phase of repolarisation was greatest with disopyramide, smaller with penticainide, and did not occur with lignocaine. Automaticity recorded in low potassium media was unaltered (disopyramide), depressed (penticainide), or stopped (lignocaine). Ionic currents were recorded in short fibres using the two microelectrode voltage clamp technique. The tetrodotoxin sensitive slow component of the sodium current was suppressed (lignocaine) or reduced (penticainide and disopyramide) and the instantaneous background potassium current slightly reduced (disopyramide more than penticainide), unaffected, or slightly increased (lignocaine). The three drugs depressed moderately and similarly the slow inward calcium current. The amplitude of the 4-aminopyridine sensitive transient outward potassium current was almost unaffected (lignocaine) or appreciably depressed (disopyramide more than penticainide). The pacemaker current was reduced greatly by lignocaine, moderately by penticainide, and slightly by disopyramide. Changes in ionic currents may explain the effects of the three drugs on action potential plateau and automaticity of sheep Purkinje fibres. It is concluded that the pronounced differences observed in the effects of these three class I antiarrhythmic drugs on pacemaker depolarisation and on initial repolarisation may justify a more discriminative subdivision of class I antiarrhythmic drugs.

Objective: The aim was to compare action potentials and ionic currents (steady state current, calcium current, calcium independent transient outward current) in two groups of trabeculae and myocytes, isolated from either dilated or non-dilated human atria. Methods: Specimens of right atrial appendage were obtained from two groups of adult patients at the time of open heart surgery, a group with non-dilated atria and a group in which right atria were clearly dilated. Action potentials were recorded with standard microelectrodes from isolated superfused trabeculae. Action potentials and ionic currents were recorded from single myocytes using the patch clamp technique in the whole cell configuration in current clamp and voltage clamp modes respectively. Results: In trabeculae taken from dilated atria the action potential was shortened and the plateau was markedly depressed compared to trabeculae taken from non-dilated atria. Similar results were obtained with single myocytes isolated from non-dilated and dilated atria. The density of the steady state current measured at the end of 0.75 s or 1 s pulses was not statistically different in the two groups of cells in the whole range of negative potentials, whereas at strongly positive potentials (>+40 mV) it was significantly reduced in cells from dilated atria compared to cells from non-dilated atria. The density of the total peak outward current was significantly reduced in cells from dilated atria [13.46(SEM 2.7) pA·pF–1 at +70 mV, n= 18] compared to cells from non-dilated atria [33.12(6.2) pA·pF–1, n = 20, p< 0.001]. The transient component of outward current was strongly depressed (at +20 mV and more positive potentials) in cells from dilated atria. The calcium current density was still more severely depressed than the total outward current in cells from dilated atria [4.46(1.06) pA·pF–1 at +20 mV, n = 26) compared to cells from non-dilated atria [17.43(1.98) pA·pF–1, n = 38, p << 0.001]. Kinetic parameters of both calcium and transient outward currents remained similar in cells from the two groups. Conclusions: The observation that in cells from dilated human atria the calcium current is more severely depressed than the total outward current can help to explain why in dilated human atria the action potential plateau is shorter and of lower amplitude than in non-dilated atria. Cardiovascular Research 1994;28:548-556

Having inactivated the sodium conductance by K-rich media, propagated slow responses were triggered by local electrical stimulation after addition of catecholamines. We determined the smallest noradrenaline concentration eliciting slow responses (noradrenaline threshold) and it was found to be 1.04 10–6mol·litre–1 ± 0.25. The rate of rise and the amplitude of cardiac slow responses increase with the external concentration in calcium, however their development is also influenced by altering potassium conductances. Substances inhibiting g_K: tetraetylammonium, 4-aminopyridine, and cesium increased the maximal rate of rise and the duration of slow responses and except for the latter compound, decreased the noradrenaline threshold. On the other hand Mg ions exerted an inhibitory effect on slow responses since they markedly decreased the maximal rate of depolarisation and increased the noradrenaline threshold in spite of a very small increase in the duration of slow responses. The effect of Mg ions can be explained by an inhibition of the slow inward current.