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

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 gK: 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. [ABSTRACT FROM PUBLISHER]

An abstract of the study "Role of Angiotensin II and Endothelin 1 in the Regulation of T-type Calcium Channels Re-expression in Cardiomyocyte," by L. P. Ferron and Y. Ruchon, is presented.

Objective: Mortality and morbidity related to right ventricular failure remain a problem for the long-term outcome of congenital heart diseases. Therapeutic innovation requires establishing an animal model reproducing right ventricular dysfunction secondary to chronic pressure-volume overload., Methods: Right ventricular tract enlargement by transvalvular patch and pulmonary artery banding were created in 2-month-old piglets (n = 6) to mimic repaired tetralogy of Fallot. Age-matched piglets were used as controls (n = 5). Right ventricular function was evaluated at baseline and 3 and 4 months of follow-up by hemodynamic parameters and electrocardiography. Right ventricular tissue remodeling was characterized using cellular electrophysiologic and histologic analyses., Results: Four months after surgery, right ventricular peak pressure increased to 75% of systemic pressure and pulmonary regurgitation significantly progressed, end-systolic and end-diastolic volumes significantly increased, and efficient ejection fraction significantly decreased compared with controls. At 3 months, the slope of the end-systolic pressure-volume relationship was significantly elevated compared with baseline and controls; a significant rightward shift of the slope, returning to the baseline value, was observed at 4 months, whereas stroke work progressed at each step and was significantly higher than in controls. Four months after surgery, QRS duration was significantly prolonged as action potential duration. Significant fibrosis and myocyte hypertrophy without myolysis and inflammation were observed in the operated group at 4 months., Conclusion: Various aspects of early right ventricular remodeling were analyzed in this model. This model reproduced evolving right ventricular alterations secondary to chronic volumetric and barometric overload, as observed in repaired tetralogy of Fallot with usual sequelae, and can be used for therapeutic innovation., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

CXCL12 (SDF-1), which binds CXCR4, is involved in several physiological and pathophysiological processes. In heart, this axis seems to play a key role in cardiogenesis and is involved in the neovascularization of ischemic tissues. Rats have three known CXCL12 mRNA isoforms, of which only alpha and gamma are present in the normal heart. However, little is known about CXCL12 protein expression and localization. We investigated the pattern of protein expression and the localization of both CXCR4 and CXCL12 in the heart, using isolated cardiomyocytes and a rat myocardial infarction model. Western blots showed that cardiomyocytes contained a specific 67-kDa CXCR4 isoform and a 12-kDa CXCL12 isoform. Confocal and electron microscopy clearly showed that CXCR4 was present at the plasmalemma and CXCL12 in continuity of the Z-line, in the proximal part of T-tubules. In conclusion, we provide the first description of the expression and fine localization of CXCR4 and CXCL12 proteins in normal rat heart and cardiomyocytes. These results suggest that the CXCL12/CXCR4 axis may be involved in cardiomyocyte calcium homeostasis regulation. Our work and the well-known chemoattraction properties of the CXCL12/CXCR4 axis highlight the importance of deciphering the function of this axis in both normal and pathological hearts.

Objectives: The aim of this study was to evaluate the myocardial consequences of a chronic volume overload of the left atrium (LA)., Background: Atrial dilation is a major risk factor for atrial fibrillation (AF), but the underlying mechanisms are poorly understood., Methods: A left-right aorto-pulmonary artery shunt (APS) was created in sheep. The cardiopathy was characterized by echocardiography, electrophysiologic testing, and histologic analysis. Cellular action potential (AP) and calcium current (I(Ca)) were recorded by means of microelectrode and patch clamp techniques., Results: Three to four months after surgery, all animals in the APS state had a dilated LA (146.2 +/- 35.4 cm(2)/m(2) vs. 91.7 +/- 10.4 cm(2)/m(2) in the control state; p = 0.0024) but remained in sinus rhythm. Repetitive atrial firing was triggered by a single extra beat in five of six animals in the APS state and in two of six animals in the control state. Moreover, in two animals in the APS state, a single extra beat triggered sustained AF. Myocytes were enlarged and 39.8% showed some degree of myolysis. In animals in the APS state, the AP had no plateau phase or small amplitude and numerous myocytes were unexcitable. The I(Ca) density was 45.2% lower in APS animals than in control animals. Beta-adrenergic stimulation normalized I(Ca) and restored the plateau phase of the AP. After shunt suppression, the electrophysiologic properties of the atria returned to normal., Conclusions: The APS induced moderate, isolated LA dilation, which was sufficient to cause major changes in cellular electrophysiologic properties and to render the atria vulnerable to fibrillation. These effects were reversed by shunt suppression.

Recent studies indicate that cardiac T-type Ca2+ current (ICaT) reappears in hypertrophied ventricular cells. The aim of this study was to investigate the role of angiotensin II (Ang II), a major inducer of cardiac hypertrophy, in the reexpression of T-type channel in left ventricular hypertrophied myocytes. We induced cardiac hypertrophy in rats by abdominal aorta stenosis for 12 weeks and thereafter animals were treated for 2 weeks with losartan (12 mg/kg per day), an antagonist of type 1 Ang II receptors (AT1). In hypertrophied myocytes, we showed that the reexpressed ICaT is generated by the CaV3.1 and CaV3.2 subunits. After losartan treatment, ICaT density decreased from 0.40+/-0.05 pA/pF (n=26) to 0.20+/-0.03 pA/pF (n=27, P<0.01), affecting CaV3.1- and CaV3.2-related currents. The amount of CaV3.1 mRNA increased during hypertrophy and retrieved its nonhypertrophic level after losartan treatment, whereas the amount of CaV3.2 mRNA was unaffected by stenosis. In cultured newborn ventricular cells, chronic Ang II application (0.1 micromol/L) also increased ICaT density and CaV3.1 mRNA amount. UO126, a mitogen-activated protein kinase kinase-1/2 (MEK1/2) inhibitor, reduced Ang II-increased ICaT density and CaV3.1 mRNA amount. Bosentan, an endothelin (ET) receptor antagonist, reduced Ang II-increased ICaT density without affecting the amount of CaV3.1 mRNA. Finally, cotreatment with bosentan and UO126 abolished the Ang II-increased ICaT density. Our results show that AT1-activated MEK pathway and autocrine ET-activated independent MEK pathway upregulate T-type channel expression. Ang II-increased of ICaT density observed in hypertrophied myocytes may play a role in the pathogenesis of Ca2+ overload and arrhythmias seen in cardiac pathology.

We studied cardiac outward K currents (transient and sustained) by the whole-cell patch-clamp technique and the Kv4.2, Kv4.3, Kv1.4, Kv1.5, Kv1.2 and Kv2.1 expression of voltage-gated K channel by RT-PCR, in ventricular myocytes from two models of catecholamine-depleted adult rats. We induced endogenous catecholamine depletion by reserpine treatment and used adrenalectomized rats as a model of plasma catecholamine depletion. In reserpine-treated rats (97% decrease in endogenous norepinephrine content of the heart), the amplitude of the transient outward current was decreased by 48% and Kv4.2 and Kv4.3 mRNA levels were decreased by 57% and 34%, respectively. The amount of Kv1.5 mRNA tripled, with no change in sustained current density. This increase was not confirmed by immunostaining for the Kv1.5 protein. The amplitude of K currents and their corresponding mRNA levels returned to control values following recovery from reserpine treatment. In contrast, in adrenalectomized rats (98% decrease in plasma epinephrine concentration), we observed no change in the amplitude of outward K currents or in Kv mRNA levels. These results suggested a role for sympathetic innervation and endogenous norepinephrine in the regulation of transcription of cardiac outward K currents in physiological and pathological situations.

T-type calcium current (I(CaT)) is distributed among a large variety of species and tissues. The main functions of I(CaT) are thought to be related to pacemaker activity and to the cell cycle. Using the whole-cell patch-clamp configuration, we showed that fetal rat ventricular cells exhibit an I(CaT) with electrophysiological and pharmacological characteristics similar to those already described for this current. We investigated I(CaT) density and found that this current was mainly expressed in fetal cells and remained stable until birth (3.1+/-0.3 pA/pF for 18-day-old fetus, n=9). I(CaT) density decreased soon after birth (2.0+/-0.3 pA/pF, n=6, 1.1+/-0.2 pA/pF, n=5, for 1- and 5-day-old rats, respectively) and was no longer detected in 21-day-old rats. The rat ventricular cells express an alpha 1H isoform in addition to a homologous alpha 1G variant. Interestingly, the Ni(2+) sensitivity of I(CaT) indicates that in newborn myocytes, I(CaT) is only generated by alpha 1G subunits, whereas both alpha 1G and alpha 1H subunits participate in the fetal I(CaT). Moreover, the relative contribution of each subunit varies during fetal developmental stages, with a major contribution of alpha 1H in 16-day-old fetuses. Through quantitative RT-PCR we showed that the amount of both alpha 1G and alpha 1H transcripts are developmentally regulated. In fetuses of less than 18 days and in newborn rats after 1 day old, the transcriptional levels of alpha 1G and alpha 1H subunits clearly mismatch the functional contribution of these subunits to I(CaT). However, in perinatal period, the amount of alpha 1G mRNA seems to be in accordance to alpha 1G-related I(CaT) density. In conclusion, we showed that I(CaT) is mainly expressed during fetal stages, that alpha 1G and alpha 1H differentially participate to I(CaT) and that alpha 1G and alpha 1H isoforms are regulated by both transcriptional and post-transcriptional mechanisms., (Copyright 2002 Academic Press.)

The effect of catecholamine depletion (induced by prior treatment with reserpine) was studied in Wistar rat ventricular myocytes using whole cell voltage-clamp methods. Two calcium-independent outward currents, the transient outward potassium current (I(to)) and the sustained outward potassium current (I(sus)), were measured. Reserpine treatment decreased tissue norepinephrine content by 97%. Action potential duration in the isolated perfused heart was significantly increased in reserpine-treated hearts. In isolated ventricular myocytes, I(to) density was decreased by 49% in reserpine-treated rats. This treatment had no effect on I(sus). The I(to) steady-state inactivation-voltage relationship and recovery from inactivation remained unchanged, whereas the conductance-voltage activation curve for reserpine-treated rats was significantly shifted (6.7 mV) toward negative potentials. The incubation of myocytes with 10 microM norepinephrine for 7-10 h restored I(to), an effect that was abolished by the presence of actinomycin D. Norepinephrine (0.5 microM) had no effect on I(to). However, in the presence of both 0.5 microM norepinephrine and neuropeptide Y (0.1 microM), I(to) density was restored to its control value. These results suggest that the sympathetic nervous system is involved in I(to) regulation. Sympathetic norepinephrine depletion decreased the number of functional channels via an effect on the alpha-adrenergic cascade and norepinephrine is able to restore expression of I(to) channels.

Objective: Cardiomyocytes can be transplanted successfully into skeletal and cardiac muscle. Our goal was to determine the feasibility of grafting cardiomyocytes onto various synthetic supports to create an excitable and viable tissue for implantation., Methods: Adult rat cardiomyocytes were cultured over an 8-week period onto different substitutes, including human glutaraldehyde-treated pericardium (n = 3), equine glutaraldehyde-treated pericardium (n = 3), polytetrafluoroethylene (n = 8), Dacron polyester (n = 16), and Vicryl polyglactin (n = 8)., Results: Only the cells seeded on the Dacron survived, with the synthetic fibers colonized at 8 weeks. On the other supports, the number of myocytes progressively decreased from the first week, with their density (number of cells per square millimeter) being, after 20 days, 17 +/- 2 on the polytetrafluoroethylene and 5 +/- 1 on the human or equine pericardium compared with 45 +/- 3 on the Dacron. After 8 weeks of culture on Dacron, the sarcomeric protein (sarcomeric alpha-actinin) was detected in all cells. In addition, the staining was regularly arranged and well aligned in a striated pattern. Spontaneous beating activity was obtained. Moreover, electrical stimulation of the cell preparation resulted in the generation of calcium transients, the frequency of which followed the frequency of the electrical stimulation., Conclusions: These results suggest that adult cardiac myocytes remain viable and excitable during long-term culture on a 3-dimensional Dacron support, which might constitute a new synthetic cardiac tissue.

The transient 4-aminopyridine-sensitive outward potassium current, Ito, is one of the ionic membrane currents involved in the repolarization of cardiac action potentials. It is present in several species (rat, dog, human) but not in guinea pig ventricle. It induces both a marked lowering of the ventricular action potential plateau level and an early repolarization wave in the ventricular ECG complex of hypothermic rats. In dog ventricle where Ito is much shorter than the action potential plateau it can induce only a transient initial repolarization (notch). The distribution of Ito is heterogeneous across the dog left ventricular free wall, the current being of sizeable amplitude in epicardial and midmyocardial layers but absent in the endocardial layer. As a result, ventricular action potentials exhibit a notch only in epicardial and mid layers. Although the physiological role of Ito remains unclear, we suggest that it can participate in the control of calcium current intensity by influencing the level of the initial part of the plateau. In pathophysiological conditions, Ito may exert unfavourable effects, specially during simulated ischemia when the notch reaches the cellular repolarization threshold, thus inducing premature termination of the action potential, an obvious cause of drastic electrical heterogeneity and resulting severe arrhythmias. The current Ito is reduced in moderate cardiac hypertrophy and dilatation and almost entirely suppressed in severe hypertrophy. Ito is of larger amplitude in human atrial than in ventricular myocytes. The heterogeneous distribution of Ito described in the dog has also been found in human ventricles. Because Ito is markedly prolonged at low temperatures it is suggested that it can be responsible for the early repolarization wave (J wave) observed in the ECG of subjects submitted to hypothermia.

Several studies have shown that the Na-Ca exchange is electrogenic in cardiac tissues and that the current carried by the exchange, iNa-Ca, participates in the development of the cardiac action potential plateau. The aim of the present study was to assess the contribution of iNa-Ca to the development of the plateau in different preparations, i.e. normal and hypertrophied (DOCA-salt) perfused rat hearts, normal and dilated (MS 200 strain) perfused hamster hearts and normal human atrial myocytes and to examine the repercussion of iNa-Ca suppression on the global electrogram of the perfused guinea-pig heart. iNa-Ca was suppressed by briefly substituting lithium for sodium (Li test). In the normal rat heart, the Li test resulted in a depression of the late component of the plateau. In the severely hypertrophied rat heart, the action potential was lengthened, the two components of the plateau barely distinguishable. The part of the plateau suppressed during Li perfusion was not larger in amplitude than in the normal rat heart, but was of much longer duration. In the dilated heart of hamsters older than 60 days of age the shortening effect of the Li test was much larger than in the normal hamster heart indicating a strongly increased contribution of iNa-Ca to the plateau development during dilatation. The contribution of iNa-Ca to the action potential plateau of human atrial myocytes was as large as that found in animal ventricles and varied with the type of cell studied. In the perfused guinea-pig heart the Li test resulted in a sizeable shortening of QT duration and a marked decrease in T wave amplitude suggesting that iNa-Ca may be a major source of current in the building up of the ventricular complex of the electrocardiogram in normal and pathological conditions.

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 Ca(2+)-independent transient outward current, Ito1. AP was recorded in perfused hearts using microelectrodes and Ito1 was 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, Ito1 density was the same in the two strains. Later on, Ito1 density 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 Ito1 from 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 Ito1 may contribute to changes in shape of AP, but cannot entirely explain dilation-induced AP lengthening.

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.

Nicorandil, a potent vasodilator substance which exerts its effects through complex mechanisms including KATP channel activation, has so far been reported to exert antiarrhythmic but not pro-arrhythmic cardiac activity. We now examined the effects of 10(-4) M nicorandil on spontaneously active or electrically driven isolated rabbit atria. Nicorandil (a) significantly reduced the action potential duration at both 50% (by approximately 45%) and 80% (by approximately 30%) repolarization and the effective refractory period (by approximately 25%) and (b) reproducibly induced short periods of tachycardia either in normal Tyrode solution after a single extra-stimulus or in low-potassium media in the absence of extra-stimulation. Quinidine (10(-5) M) or the KATP channel inhibitor, tolbutamide (10(-5) M), suppressed the nicorandil-induced arrhythmias. It is suggested that the pro-arrhythmic effect of nicorandil results from its KATP channel opener activity and occurs essentially when the underlying conditions facilitate re-entry.

The effect of 2,3-butanedione 2-monoxime (BDM), a substance possessing phosphatase-like activity, was studied on action potentials of isolated rat heart and on the slow inward calcium current and outward current (including the 4-aminopyridine (4-AP)-sensitive transient outward component), in rat ventricular myocytes. In contrast to what was observed by other authors in different species and cardiac tissues, BDM increased markedly the amplitude and duration of the rat ventricular action potential plateau. On the other hand, in the presence of 4-AP and ryanodine BDM shortened action potential duration. BDM decreased in a dose dependent manner the amplitude of both the slow inward calcium current and the transient outward current, accelerated their inactivation and shifted their steady-state inactivation-voltage relationships towards negative potentials. BDM also depressed other components of outward current. It is suggested that the lengthening effect of BDM on action potential duration results mainly from the simultaneous reduction of both the slow inward calcium current and the transient outward current, two antagonistic currents with unequal influences on action potential plateau development. The similarity of effect of BDM on these two currents also suggests that ionic channels generating them might require similar phosphorylation for their functioning.

Maitotoxin (MTX) irreversibly suppressed the voltage-dependent calcium current after a variable delay, an effect which was preceded, in 61% of the cells, by a transient increase in calcium current partly attributable to a shift (4-7 mV) of the activation curve towards negative potentials. MTX also induced the development of a voltage-independent background inward current which did not occur in the absence of external calcium and was reduced by removal of external sodium, by calcium channel blockers and by high concentrations of quinidine. MTX-induced single channel activity consisted of long lasting bursts of inward current. Channel activity was voltage-independent, with a unitary conductance of 14 pS and an extrapolated reversal potential of +16 mV. Single-channel current amplitude was not detectably reduced in the absence of external calcium but strongly reduced in the absence of external sodium, in the presence of 2 mM nickel or when external sodium was replaced by 96 mM calcium or 50 mM barium. The channel activity was also inhibited by quinidine. It is concluded that MTX alters, then suppresses the voltage-activated calcium current and induces the development of a voltage-independent inward current, part of which results from the opening of nickel-sensitive cation channels, mostly permeable to sodium ions.

Equations described by Mc Allister et al. (1975) were used to simulate the abnormal repolarization phase of the action potential (early after depolarization or hump), which often occurs in isolated dog Purkinje fibers submitted to acid media and can result in re-excitation. The development of humps was simulated by modifying the īK2-Em relationship in such a way that the resulting repolarizing current was increased at low membrane potential and decreased at higher (more negative) membrane potential. Beyond a certain size, humps triggered single, or multiple re-excitations. Hump size was very sensitive to small changes in īK2 and iK1, moderately sensitive to changes in īx1 and almost insensitive to changes in ix2. Negative shifts in the s infinity-Em relationship induced slowing of the basic frequency and only a small decrease in hump size. Decreasing gsi and gNa exerted inhibitory effects on hump development, the latter effect being larger than the former. The steady-state inward sodium current resulting from the overlap of m infinity-Em and h infinity-Em relationships appeared of particular importance in the development of humps.

The major ionic conductances underlying electrical activity in cardiac tissues are described. The participation of electrogenic active transport in electrical phenomenon and the influence of metabolic inhibition on cardiac action potentials are briefly summarized. Some electrophysiological effects of lactate and acidosis, such as might be induced by ischemia, are described. In dog Purkinje fibers, lactate (20 mM pH 7.0) may induce transient periods of arrhythmias. Acidosis decreases rapid sodium conductance, slow calcium-sodium conductance, and anomalous and delayed rectifications in frog atrial fibers. CO2-induced acidosis (20% CO2, pH 6.6) may alter the repolarization phase of the action potential in dog Purkinje fibers, presumably because it decreases potassium conductance. Alterations consist of partial depolarizations (humps) that result in reexcitation of the fibers and lead to a maintained depolarization. It is proposed that acidosis induces a decrease in potassium conductance that can be responsible for ectopic foci causing arrhythmias during ischemia.

Electrical activity of rat atrium of streptozotocin-diabetic and control rats was compared. (i) As occurs in the ventricle, diabetes lengthens the cardiac atrial action potential. (ii) Treatment by T3 of diabetic animals decreases action potential duration to normal values and causes partial recovery in plateau decay during the late phase of repolarization. (iii) T3 treatment however, does not completely normalized the action potential of the diabetic rat atrium, which remains abnormal during the early phase of repolarization. These results demonstrate that some defects in membrane mechanisms involved in the early phase of action potential repolarization are attributable solely to diabetes. The possible nature of these mechanisms is discussed.

The electrophysiological, inotropic and chronotropic effects of the two first natural amino-dexoyglyco-cardenolides, mitiphylline and holarosine B, were studied. Mitiphylline has qualitatively the same properties as those of common cardiac glycosides but is more potent; holarosine B has a similar action on cardiac electrophysiological parameters of the guinea pig heart but is less potent. The difference in activity between these two compounds could be attributed to the configuration in 5-and 17-positions of the genins. Holarisone B has the particularity of increasing the action potential plateau amplitude and its duration in rat heart; this could be part of the role of the aminosugar moiety.