16 results on '"Lederer, W. J."'
Search Results
2. Ni2+ transport by the human Na+/Ca2+ exchanger expressed in Sf9 cells.
- Author
-
Egger M, Ruknudin A, Niggli E, Lederer WJ, and Schulze DH
- Subjects
- Aniline Compounds, Animals, Baculoviridae genetics, Biological Transport, Calcium pharmacology, Calcium Radioisotopes metabolism, Fluorescent Dyes, Humans, Nickel pharmacology, Transfection, Xanthenes, Gene Expression, Nickel metabolism, Sodium-Calcium Exchanger genetics, Sodium-Calcium Exchanger metabolism, Spodoptera metabolism
- Abstract
The mechanism of Ni2+ block of the Na+/Ca2+ exchanger was examined in Sf 9 cells expressing the human heart Na+/Ca2+ exchanger (NCX1-NACA1). As predicted from the reported actions of Ni2+, its application reduced extracellular Na+-dependent changes in intracellular Ca2+ concentration (measured by fluo 3 fluorescence changes). However, contrary to expectation, the reduced fluorescence was accompanied by measured 63Ni2+ entry. The 63Ni2+ entry was observed in Sf 9 cells expressing the Na+/Ca2+ exchanger but not in control cells. The established sequential transport mechanism of the Na+/Ca2+ exchanger could be compatible with these results if one of the two ion translocation steps is blocked by Ni2+ and the other permits Ni2+ translocation. We conclude that, because Ni2+ entry was inhibited by extracellular Ca2+ and enhanced by extracellular Na+, the Ca2+ translocation step moved Ni2+, whereas the Na+ translocation step was inhibited by Ni2+. A model is presented to discuss these findings.
- Published
- 1999
- Full Text
- View/download PDF
3. Independent inhibition of calcineurin and K+ currents by the immunosuppressant FK-506 in rat ventricle.
- Author
-
duBell WH, Gaa ST, Lederer WJ, and Rogers TB
- Subjects
- Animals, Calcineurin physiology, Calcium metabolism, Cell Separation, Cyclosporine pharmacology, Electric Conductivity, Heart Ventricles, Homeostasis, Intracellular Membranes metabolism, Myocardium cytology, Myocardium metabolism, Osmolar Concentration, Potassium physiology, Rats, Rats, Sprague-Dawley, Calcineurin Inhibitors, Heart drug effects, Immunosuppressive Agents pharmacology, Potassium antagonists & inhibitors, Tacrolimus pharmacology
- Abstract
FK-506 increases the cytosolic Ca2+ concentration transient in rat ventricular myocytes by prolonging the action potential through inhibition of the K+ currents Ito and IK [J. Physiol. (Lond.) 501: 509-516, 1997]. Physiological and biochemical techniques were used in parallel to examine the electrophysiological mechanisms and the role of calcineurin inhibition in these effects. FK-506 prolonged the recovery of Ito from inactivation. Thus Ito inhibition was frequency dependent, with no decrease at 0.2 Hz (recorded at +50 mV from -70 mV) but a 40% decrease at 2.0 Hz. In contrast, inhibition of IK ( approximately 60%) was time and voltage independent. At 25 microM, FK-506 (by 65%) and cyclosporin A (by 57%) inhibited calcineurin activity in myocyte extracts. However, only FK-506 increased the cytosolic Ca2+ concentration transient in field-stimulated myocytes. Furthermore, FK-506 was still active on K+ currents when cells were dialyzed with 10 mM EGTA. These results demonstrate that calcineurin inhibition is not responsible for the functional effects of FK-506 in heart and suggest that IK and Ito are modulated by FK-506-binding proteins or directly by FK-506.
- Published
- 1998
- Full Text
- View/download PDF
4. Na+/Ca2+ exchanger in Drosophila: cloning, expression, and transport differences.
- Author
-
Ruknudin A, Valdivia C, Kofuji P, Lederer WJ, and Schulze DH
- Subjects
- Alternative Splicing, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins chemistry, Cell Membrane physiology, Cloning, Molecular, Consensus Sequence, Cyclic AMP-Dependent Protein Kinases metabolism, DNA, Complementary metabolism, Drosophila genetics, Genes, Insect, Genomic Library, Humans, In Situ Hybridization, Mammals, Molecular Sequence Data, Oocytes physiology, Phosphorylation, Protein Kinase C metabolism, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Sodium-Calcium Exchanger, Xenopus, Carrier Proteins genetics, Carrier Proteins metabolism, Chromosome Mapping, DNA, Complementary chemistry, Drosophila metabolism
- Abstract
cDNAs for the Na+/Ca2+ exchanger from Drosophila melanogaster (Dmel/Nck) have been cloned by homology screening using the human heart Na+/Ca2+ exchanger cDNA. The overall deduced protein structure for Dmel/Nck is similar to that of mammalian Na+/Ca2+ exchanger genes NCX1 and NCX2, having six hydrophobic regions in the amino terminus separated from six at the carboxy-terminal end by a large intracellular loop. Sequence comparison of the Drosophila exchanger cDNAs with NCX1 and NCX2 Na+/Ca2+ exchangers are approximately 46% identical at the deduced amino acid level. Consensus phosphorylation sites for both protein kinase C and protein kinase A are present on the intracellular loop region of the Dmel/Nck. Alternative splicing for the Dmel/Nck gene is suggested in the same intracellular loop region as demonstrated for NCX1. Functionally, the Drosophila Na+/ Ca2+ exchanger expressed in oocytes differs from expressed mammalian NCX1 with regard to Ca2+ transport in Ca2+/ Ca2+ exchange and the effect of monovalent-dependent Ca2+/ Ca2+ exchange. The Dmel/Nck gene maps to chromosome 3 (93A-B) using in situ hybridization to polytene chromosomes, the same position as the Na(+)-K(+)-ATPase, a related transporter. We conclude that, although extracellular Na+ concentration-dependent Ca2+ transport is subserved by both human and Drosophila Na+/Ca2+ exchangers, there are clear and important differences in the transporters, which should be useful in deducing how the Na+/Ca2+ exchanger protein function depends on its structure.
- Published
- 1997
- Full Text
- View/download PDF
5. A chloride current component induced by hypertrophy in rat ventricular myocytes.
- Author
-
Bénitah JP, Gómez AM, Delgado C, Lorente P, and Lederer WJ
- Subjects
- Animals, Anthracenes pharmacology, Barium pharmacology, Chloride Channels antagonists & inhibitors, Electric Conductivity, Male, Membrane Potentials, Myocardium cytology, Rats, Rats, Sprague-Dawley, Chlorides physiology, Heart physiopathology, Hypertrophy, Left Ventricular physiopathology
- Abstract
The effect of hypertrophy on membrane currents of rat left ventricular myocytes was studied with the whole cell voltage-clamp method. We found that the slope of the total time-independent current density-voltage relationship was increased in hypertrophied cells. No change in the zero-current potential was observed. Surprisingly, the dominant time-independent current, the inward rectifier K+ current (measured as the Ba(2+)-sensitive current density) was unchanged. We therefore investigated the identity of the outwardly rectifying Ba(2+)-resistant current seen in the hypertrophied rat ventricular myocytes but not present in control cells. We found that this current 1) was not carried by monovalent cations, 2) was partially blocked by anthracene-9-carboxylic acid (9-AC), and 3) was sensitive to variations in extracellular Cl concentration. These findings are consistent with the current being carried at least partially by Cl-. The presence of an additional Cl(-)-dependent component in hypertrophied cells is supported by the actions of 9-AC on the measured action potentials (APs). 9-AC had no effect on control cells APs but prolonged hypertrophied cell APs. We conclude that a Cl- current component develops in hypertrophied rat heart cells. This component appears to shorten the AP duration and might thus provide protection from cardiac arrhythmias.
- Published
- 1997
- Full Text
- View/download PDF
6. Calcium sparks and [Ca2+]i waves in cardiac myocytes.
- Author
-
Cheng H, Lederer MR, Lederer WJ, and Cannell MB
- Subjects
- Animals, Electrophysiology, Image Processing, Computer-Assisted, Microscopy, Confocal, Microscopy, Electron, Myocardium cytology, Osmolar Concentration, Rats, Sarcoplasmic Reticulum metabolism, Time Factors, Calcium metabolism, Intracellular Membranes metabolism, Myocardium metabolism
- Abstract
Local elevations in intracellular calcium ("Ca2+ sparks") in heart muscle are elementary sarcoplasmic reticulum (SR) Ca(2+)-release events. Ca2+ sparks occur at a low rate in quiescent cells but can also be evoked by electrical stimulation of the cell to produce the cell-wide Ca2+ transient. In this study we investigate how Ca2+ sparks are related to propagating waves of elevated cytosolic Ca2+ induced by "Ca2+ overload." Single ventricular myocytes from rat were loaded with the Ca(2+)-sensitive indicator fluo 3 and imaged with a confocal microscope. After extracellular Ca2+ concentration was increased from 1 to 10 mM to produce Ca2+ overload, the frequency of spontaneous Ca2+ sparks, which occur at the t tubule/SR junction, increased approximately 4-fold, whereas the spark amplitude and spatial size increased 4.1-and 1.7-fold, respectively. In addition, a spectrum of larger subcellular events, including propagating Ca2+ waves, was observed. Ca2+ sparks were seen to occur at the majority (65%) of the sites of wave initiation. For slowly propagating Ca2+ waves, discrete Ca(2+)-release events, similar to Ca2+ sparks, were detected in the wave front. These Ca2+ sparks appeared to recruit other sparks along the wave front so that the wave progressed in a saltatory manner. We conclude that Ca2+ sparks are elementary events that can explain both the initiation and propagation of Ca2+ waves. In addition, we show that Ca2+ waves and electrically evoked Ca2+ transients have the same time course and interact with each other in a manner that is consistent with both phenomena having the same underlying mechanism(s). These results suggest that SR Ca2+ release during Ca2+ waves, like that during normal excitation-contraction coupling, results from the spatial and temporal summation of Ca2+ sparks.
- Published
- 1996
- Full Text
- View/download PDF
7. Nifedipine inhibits movement of cardiac calcium channels through late, but not early, gating transitions.
- Author
-
Hadley RW and Lederer WJ
- Subjects
- Animals, Calcium Channels metabolism, Electrophysiology, Guinea Pigs, Light, Myocardium cytology, Nifedipine antagonists & inhibitors, Time Factors, Calcium Channel Blockers pharmacology, Calcium Channels drug effects, Ion Channel Gating drug effects, Myocardium metabolism, Nifedipine pharmacology
- Abstract
L-type Ca2+ channels were studied in guinea pig ventricular myocytes by examining how photoinactivation of nifedipine affected the Ca2+ current (ICa) and the Ca2+ channel gating current (Ig). ICa, blocked by nifedipine, reappeared in qualitatively different phases (immediate and delayed) following photoinactivation of nifedipine. Immediate recovery was attributed to unblock of closed Ca2+ channels, while delayed recovery was attributed to unblock of inactivated channels. In contrast to the ICa results, photoinactivation of nifedipine produced only delayed recovery of Ig. Analysis of these results suggests the following conclusions. First, the actions of inhibitory dihydropyridines can be attributed to binding to either the inactivated or the closed conformation, but only binding to the inactivated state is associated with reduction of Ig. Second, the action of inhibitory dihydropyridines on closed channels is to retard their movement through a final, voltage-independent transition to the open state. This effect seems to be the converse of a major action of stimulatory dihydropyridines and thus is the principal mechanistic difference between stimulatory and inhibitory dihydropyridines.
- Published
- 1995
- Full Text
- View/download PDF
8. A confocal laser scanning microscope designed for indicators with ultraviolet excitation wavelengths.
- Author
-
Niggli E, Piston DW, Kirby MS, Cheng H, Sandison DR, Webb WW, and Lederer WJ
- Subjects
- Animals, Calcium metabolism, Fluorescent Dyes, Guinea Pigs, Indoles, Microspheres, Myocardium cytology, Myocardium metabolism, Optics and Photonics, Indicators and Reagents, Lasers, Microscopy methods, Ultraviolet Rays
- Abstract
In this paper we describe the modifications necessary to upgrade, at affordable cost, a commercially available confocal laser scanning microscope for use with ultraviolet (UV) excitation. The optical problems associated with these modifications are described in detail, and easy solutions to solve them are suggested. The optical resolution of the instrument was tested with fluorescent beads and was found to be close to diffraction limited. The light losses due to lateral chromatic aberration were assessed in a thick fluorescent specimen and were found to be comparable to those usually observed with visible light. For a more visual example of the resolution of this instrument, isolated ventricular heart muscle cells were loaded with the fluorescent Ca2+ indicator indo 1. This allowed us to visualize subcellular structural detail and to illustrate the optical sectioning capability of the UV confocal microscope when recording indo 1 emission. Dual-emission line scans were used to perform ratiometric time-resolved detection of Ca2+ transients in voltage-clamped heart muscle cells loaded with the salt form of indo 1. The system presented in this paper should significantly broaden the range of fluorescent indicators that can be used in confocal microscopy.
- Published
- 1994
- Full Text
- View/download PDF
9. Na/Ca exchanger isoforms expressed in kidney.
- Author
-
Kofuji P, Lederer WJ, and Schulze DH
- Subjects
- Animals, Base Sequence, Carrier Proteins genetics, Isomerism, Molecular Probes genetics, Molecular Sequence Data, Nucleic Acid Hybridization, Polymerase Chain Reaction, RNA-Directed DNA Polymerase, Rabbits, Ribonucleases, Sodium-Calcium Exchanger, Carrier Proteins metabolism, Kidney metabolism
- Abstract
The cardiac (versus retinal rod) Na/Ca exchanger gene has been cloned, sequenced and shown by RNA analysis to be present in diverse tissues. Analysis of published sequences shows that a single isoform is found in heart tissue from many species (NACA1 isoform). We provide evidence here by ribonuclease (RNase) protection assays and by reverse transcriptase-polymerase chain reaction (PCR) amplification with sequence analysis that a new isoform encoding the Na/Ca exchanger is present in renal tissue. This isoform (NACA3) reveals a 7-amino acid deletion in the tested region compared with the NACA2 isoform described by Reilly and Shugrue [Am. J. Physiol. 262 (Renal Fluid Electrolyte Physiol. 31): F1105-F1109, 1992] and is the dominant exchanger transcript in kidney. Analysis of the sequence of all isoforms indicates that the differences in the isoforms reside in the large intracellular loop region of the protein. Alternative splicing of a single Na/Ca exchanger message may be responsible for these tissue-specific transcripts.
- Published
- 1993
- Full Text
- View/download PDF
10. Expression of the Na-Ca exchanger in diverse tissues: a study using the cloned human cardiac Na-Ca exchanger.
- Author
-
Kofuji P, Hadley RW, Kieval RS, Lederer WJ, and Schulze DH
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Blotting, Southern, Calcium metabolism, Carrier Proteins genetics, Cloning, Molecular, Electrophysiology, Humans, Molecular Sequence Data, Nucleic Acid Hybridization, Oligonucleotide Probes genetics, Rats, Ribonucleases, Sodium pharmacology, Sodium-Calcium Exchanger, Transcription, Genetic, Carrier Proteins metabolism
- Abstract
In many cells including cardiac myocytes, cytoplasmic Ca is importantly controlled by the plasmalemmal Na-Ca exchanger (3, 8). The tissue diversity and differences in cellular environment raise the question whether the same exchanger is found in all tissues. Recent experiments using rod cells have demonstrated that at least two forms of Na-dependent Ca transport exist. We have examined this issue in various rat and human tissues using the cloned human cardiac Na-Ca exchanger cDNA. Northern blot analysis in these two species show that the major transcript of the Na-Ca exchanger is 7.2 kilobases in heart, brain, kidney, liver, pancreas, skeletal muscle, placenta, and lung. Furthermore, ribonuclease protection analysis in rats shows conservation of the 348-base pair segment tested in heart, brain, kidney, skeletal muscle, and liver. Additionally, Southern blot analysis suggests that a single gene encodes this Na-Ca exchanger. Finally, we show that the clone used to generate our probes encodes a completely functional Na-Ca exchanger. With the use of COS cells and 293 cells transfected with the cloned human cardiac Na-Ca exchanger, we tested the Ca transport properties of the Na-Ca exchanger, the voltage dependence of the Na-Ca exchanger, as well as the Na dependence of the transport function of the Na-Ca exchanger. We conclude that the cardiac form of the Na-Ca exchanger is completely functional when the cDNA is expressed in mammalian cell lines, and, furthermore, this "cardiac" form of the Na-Ca exchanger is naturally expressed in all human and rat tissues tested (but at varying levels).
- Published
- 1992
- Full Text
- View/download PDF
11. Immunofluorescence localization of the Na-Ca exchanger in heart cells.
- Author
-
Kieval RS, Bloch RJ, Lindenmayer GE, Ambesi A, and Lederer WJ
- Subjects
- Animals, Fluorescent Antibody Technique, Immunoblotting, Microscopy, Fluorescence, Myocardium cytology, Myocardium ultrastructure, Sodium-Calcium Exchanger, Subcellular Fractions metabolism, Tissue Distribution, Carrier Proteins metabolism, Myocardium metabolism
- Abstract
We investigated the localization of the Na-Ca exchanger in fixed, isolated heart cells from rat and guinea pig using immunocytochemical methods with epifluorescence and confocal microscopy. We found that the Na-Ca exchanger is distributed throughout all membranes in contact with the extracellular space, including the sarcolemma, the transverse tubules (T-tubules), and the intercalated disks. Microscopic nonuniformities in the fluorescent labeling appear to reflect varying views of the membranes containing Na-Ca exchanger protein. Confocal thin-section imaging reveals a regular grid of discrete foci of fluorescence, which represent Na-Ca exchanger in T-tubules viewed en face. These foci are 1.80 +/- 0.01 microns apart from sarcomere to sarcomere and are aligned with the Z-line. Along each Z-line, these foci are spaced at 1.22 +/- 0.11-microns intervals. Longitudinal sections of the sarcolemma-T-tubule junction show a comblike appearance, with T-tubules extending inward from the heavily labeled sarcolemma. Our finding that the Na-Ca exchanger is widely distributed over the cell surface may provide further insight into the role of Na-Ca exchange in the heart.
- Published
- 1992
- Full Text
- View/download PDF
12. Comparison of the effects of BAY K 8644 on cardiac Ca2+ current and Ca2+ channel gating current.
- Author
-
Hadley RW and Lederer WJ
- Subjects
- Animals, Electric Conductivity, Electrophysiology, 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester pharmacology, Calcium physiology, Calcium Channels physiology, Heart physiology, Ion Channel Gating
- Abstract
Effects of (-)-BAY K 8644 on Ca2+ channel function were studied in guinea pig ventricular myocytes. It was found that the compound has both voltage-dependent stimulatory and inhibitory effects on the Ca2+ current (ICa), in agreement with prior studies. The basis for these effects was studied by evaluating the effects of (-)-BAY K 8644 on the Ca2+ channel gating current. It was found that the voltage-dependent inhibitory effects of the drug on ICa could be well explained by similar reductions in the amount of gating charge moved. However, the stimulatory effect of (-)-BAY K 8644 on ICa could not be simply correlated with changes in the amount of gating charge moved. Although the drug produced a shift of the charge-voltage relationship to more negative potentials, the drug actually reduced the total amount of movable gating charge. Thus it could be demonstrated that there are membrane potentials where (-)-BAY K 8644 reduced the Ca2+ channel gating current while enhancing ICa. In addition, the drug was found to slow the decay of the gating current during repolarization. It seems likely that (-)-BAY K 8644 has a dual effect on Ca2+ channels: affecting both the voltage dependence of gating charge and the relationship between open probability and charge movement.
- Published
- 1992
- Full Text
- View/download PDF
13. Adenosine triphosphate-sensitive potassium channels in the cardiovascular system.
- Author
-
Nichols CG and Lederer WJ
- Subjects
- Animals, Cardiovascular Diseases physiopathology, Humans, Adenosine Triphosphate pharmacology, Cardiovascular Physiological Phenomena, Potassium Channels physiology
- Abstract
ATP is normally available in cells at millimolar concentrations and is "buffered" by intracellular pools of other high-energy phosphates, such as creatine phosphate. Thus intracellular [ATP] [( ATP]i) may seem an unlikely candidate for a regulatory signal inside cells. Recent evidence suggests, however, that [ATP]i regulates the behavior of a class of potassium (KATP) channels that are found throughout the cardiovascular system. KATP channels are present in cardiac, skeletal, and vascular smooth muscle. The channels are inhibited by micromolar [ATP]i, and this inhibition is relieved by micromolar [ADP]i. We present evidence in support of the idea that variations of [ATP]i and [ADP]i, even within normal concentration ranges, may influence cellular function in the heart and vascular system via a direct action on the KATP channel. Furthermore, very specific modulators of KATP channel activity are available. We discuss the mechanism of action of these agents and their interaction with endogenous modulators and consider their potential roles in cardiovascular therapy.
- Published
- 1991
- Full Text
- View/download PDF
14. Intracellular Ca transients in rat cardiac myocytes: role of Na-Ca exchange in excitation-contraction coupling.
- Author
-
Bers DM, Lederer WJ, and Berlin JR
- Subjects
- Animals, Cells, Cultured, Fluorescent Dyes, Heart drug effects, Heart physiology, Indoles, Kinetics, Rats, Sodium pharmacology, Sodium-Calcium Exchanger, Spectrometry, Fluorescence, Calcium metabolism, Carrier Proteins metabolism, Myocardial Contraction, Myocardium metabolism, Sodium metabolism
- Abstract
Membrane current and intracellular Ca concentration ([Ca]i) transients were recorded from isolated rat ventricular myocytes under voltage-clamp control. The cells were dialyzed by the patch pipette solution, which contained the fluorescent Ca indicator indo-1 and 0.5 mM Na. Under these experimental conditions, Ca entry via Na-Ca exchange did not appear to be appreciable even in the absence of extracellular Na. Increasing the duration of voltage-clamp pulses from 5 to 80 ms produced [Ca]i transients of increasing amplitude, while the peak Ca current was not changed. This duration dependence of the [Ca]i transient was most demonstrable at more negative test potentials (e.g., -20 to -30 mV) and was not qualitatively modified by Na-free solutions. This latter result indicates that Ca extrusion by Na-Ca exchange is not responsible for the smaller [Ca]i transients observed when the membrane is repolarized after very brief depolarizations. Although the peak Ca current was not changed by increasing pulse duration, the integrated Ca current was increased. These observations are consistent with a Ca-release mechanism in cardiac excitation-contraction coupling in which 1) the Ca-release process can be modulated by membrane potential or 2) the Ca entering the cell via Ca channels has a preferential access [compared with Ca from the sarcoplasmic reticulum (SR)] to the site(s) that control SR Ca release. The role of Na-Ca exchange in the decline of [Ca]i during relaxation was also explored. Removal of extracellular Na (Nao) resulted in 20% slowing of the decline in [Ca]i during relaxation. From this, we conclude that the Na-Ca exchange competes with SR to remove Ca from the cytoplasm and that under our control conditions the exchanger may account for 20% of this decline. The Nao dependence of relaxation was reduced at more positive membrane potentials and increased by SR Ca loading.
- Published
- 1990
- Full Text
- View/download PDF
15. Regulation of twitch tension in sheep cardiac Purkinje fibers during calcium overload.
- Author
-
Berlin JR, Cannell MB, and Lederer WJ
- Subjects
- Animals, Caffeine pharmacology, Electric Stimulation, Gallopamil pharmacology, Myocardial Contraction, Sheep, Time Factors, Calcium pharmacology, Heart Conduction System physiology, Purkinje Fibers physiology
- Abstract
The dependence of twitch tension on the interval (delta t) between depolarizations was examined in voltage-clamped sheep cardiac Purkinje fibers under conditions of calcium overload. During the development of calcium overload (produced by sodium-pump inhibition), twitch amplitude changes from a monotonic function of delta t to an oscillatory one. We investigated the cellular processes underlying this oscillatory relationship. Measurable calcium current was blocked by D 600 (25 microM), but neither the twitch nor the oscillatory dependence of twitch tension on delta t was abolished. Caffeine (2 mM), applied to modify sarcoplasmic reticulum function, decreased the oscillatory period of the twitch/interval relationship as it increased the frequency of spontaneous fluctuations of resting tension. Our results suggest that the oscillatory relationship between twitch amplitude and delta t is not caused by changes in the calcium current per se but rather by fluctuations in the amount of releasable calcium in the sarcoplasmic reticulum. Additionally, we conclude that the calcium current may not be a necessary prerequisite for depolarization to trigger calcium release from the sarcoplasmic reticulum under conditions of calcium overload.
- Published
- 1987
- Full Text
- View/download PDF
16. Na-Ca exchange: stoichiometry and electrogenicity.
- Author
-
Eisner DA and Lederer WJ
- Subjects
- Action Potentials, Animals, Biological Transport, Active, Caffeine pharmacology, Cells, Cultured, Electrochemistry, Humans, Ion Channels drug effects, Ion Channels metabolism, Ion Exchange, Mathematics, Membrane Potentials, Models, Chemical, Calcium metabolism, Ion Channels physiology, Sodium metabolism
- Abstract
This review discusses the evidence concerning the stoichiometry of Na-Ca exchange. In particular we consider whether the Na-Ca exchange has been shown to transport more than two Na+ ions per Ca2+ ion and therefore whether it generates an electric current. The first part of this review discusses both direct and indirect evidence concerning the stoichiometry of the exchange and its possible voltage dependence. We find that, although there is some evidence suggesting that more than two Na+ ions may exchange for each Ca2+ ion, most of the available evidence is equivocal and cannot fix the stoichiometry precisely. Furthermore, using a simple and explicit circulating carrier model for the Na-Ca exchange, we show that the effect of membrane potential on the Na-Ca exchange may be considerably more complicated than is generally believed. In particular we find that both electrogenic and electroneutral exchanges will be affected by membrane potential. We therefore conclude that the demonstration of the voltage dependence of the Na-Ca exchange does not necessarily imply that it is electrogenic. Additionally, this analysis shows that, apart from a restricted range near thermodynamic equilibrium, it is impossible to predict either the magnitude or the direction of the effects of membrane potential on the exchange. In the second part of the review we consider whether any known membrane currents may be attributed to Na-Ca exchange. We show, in contrast to previous suggestions, that the Na-Ca exchange can theoretically produce a current that appears to be activated by intracellular Ca and that has a reversal potential. However, the experimental demonstration that a given current is produced by Na-Ca exchange is hampered by the existence of other Ca- and Na-dependent currents. In conclusion, we feel that there is no evidence that allows any particular membrane current to be unambiguously identified with the Na-Ca exchange.
- Published
- 1985
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.