The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
Allan J. Levi - One of the best experts on this subject based on the ideXlab platform.
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A role for sodium/calcium exchange in the action potential shortening caused by strophanthidin in guinea pig ventricular myocytes
Cardiovascular Research, 1993Co-Authors: Allan J. LeviAbstract:Objective: The aim was to investigate the nature of the Membrane Currents which underlie the shortening of the action potential in guinea pig cardiac myocytes upon exposure to the digitalis analogue strophanthidin. Methods: Ventricular myocytes were isolated enzymatically from the guinea pig heart and impaled with conventional microelectrodes to measure action potentials. Cells were voltage clamped and the change in Membrane Current upon strophanthidin exposure was recorded. Contractile activity was assessed optically as cell shortening. Results: Strophanthidin caused an initial lengthening followed by a progressive shortening of the action potential. The initial lengthening was due to an inhibition of outward Na/K pump Current caused by strophanthidin. The subsequent action potential shortening was associated with the progressive activation of a Membrane Current that reversed at −54.5(SD 7.5) mV, n=8. Since this Current was outward over the potential range of the action potential plateau, it participated in causing the action potential shortening with strophanthidin. This component of Membrane Current was not sensitive to potassium channel blockers, but it was blocked by removing external Ca and applying 5 mM nickel externally. Removal of external Ca inhibits outward Current generated by the Ca entry/Na extrusion mode of the Na/Ca exchange, whereas nickel is known to block the Na/Ca exchange. Conclusions: The voltage dependence of the Membrane Current associated with progressive action potential shortening, and its sensitivity to external Ca and nickel, suggest that it is carried on the Na/Ca exchange. It is proposed that the Na/Ca exchange generates this Membrane Current in response to the combined rise of intracellular sodium and calcium that occurs with strophanthidin. Theoretical calculations simulating the effect of a combined rise of intracellular sodium and calcium on Na/Ca exchange predict closely the reversal potential and characteristics of the experimentally measured Current. The results of this study suggest that a Membrane Current generated by the Na/Ca exchange makes an important contribution to the action potential shortening that occurs with digitalis compounds. Cardiovascular Research 1993; 27 :471-481
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a role for sodium calcium exchange in the action potential shortening caused by strophanthidin in guinea pig ventricular myocytes
Cardiovascular Research, 1993Co-Authors: Allan J. LeviAbstract:Objective: The aim was to investigate the nature of the Membrane Currents which underlie the shortening of the action potential in guinea pig cardiac myocytes upon exposure to the digitalis analogue strophanthidin. Methods: Ventricular myocytes were isolated enzymatically from the guinea pig heart and impaled with conventional microelectrodes to measure action potentials. Cells were voltage clamped and the change in Membrane Current upon strophanthidin exposure was recorded. Contractile activity was assessed optically as cell shortening. Results: Strophanthidin caused an initial lengthening followed by a progressive shortening of the action potential. The initial lengthening was due to an inhibition of outward Na/K pump Current caused by strophanthidin. The subsequent action potential shortening was associated with the progressive activation of a Membrane Current that reversed at −54.5(SD 7.5) mV, n=8. Since this Current was outward over the potential range of the action potential plateau, it participated in causing the action potential shortening with strophanthidin. This component of Membrane Current was not sensitive to potassium channel blockers, but it was blocked by removing external Ca and applying 5 mM nickel externally. Removal of external Ca inhibits outward Current generated by the Ca entry/Na extrusion mode of the Na/Ca exchange, whereas nickel is known to block the Na/Ca exchange. Conclusions: The voltage dependence of the Membrane Current associated with progressive action potential shortening, and its sensitivity to external Ca and nickel, suggest that it is carried on the Na/Ca exchange. It is proposed that the Na/Ca exchange generates this Membrane Current in response to the combined rise of intracellular sodium and calcium that occurs with strophanthidin. Theoretical calculations simulating the effect of a combined rise of intracellular sodium and calcium on Na/Ca exchange predict closely the reversal potential and characteristics of the experimentally measured Current. The results of this study suggest that a Membrane Current generated by the Na/Ca exchange makes an important contribution to the action potential shortening that occurs with digitalis compounds. Cardiovascular Research 1993; 27 :471-481
Luigia Santella - One of the best experts on this subject based on the ideXlab platform.
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Ca^2+ signalling and Membrane Current activated by cADPr in starfish oocytes
Pflügers Archiv, 2003Co-Authors: Francesco Moccia, Gilda A. Nusco, Dmitri Lim, Emanuela Ercolano, Gianni Gragnaniello, Euan R. Brown, Luigia SantellaAbstract:Cyclic ADP-ribose (cADPr) is a second messenger that regulates intracellular free [Ca^2+] ([Ca^2+]_i) in a variety of cell types, including immature oocytes from the starfish Astropecten auranciacus . In this study, we employed confocal laser scanning microscopy and voltage clamp techniques to investigate the source of the cADPr-elicited Ca^2+ wave originating from the cortical Ca^2+ patches we have described previously. The Ca^2+ swing was accompanied by a Membrane Current with a reversal potential of ≈+20 mV. Decreasing external Na^+ almost abolished the Current without affecting the Ca^2+ response. Removal of extracellular Ca^2+ altered neither the Ca^2+ transient nor the ionic Current, nor did the holding potential exert any effect on the Ca^2+ wave. Both the Ca^2+ response and the Membrane Current were abolished when BAPTA, ruthenium red or 8-NH_2-cADPr were preinjected into the oocytes, while perfusion with ADPr did not elicit any [Ca^2+]_i increase or ionic Current. However, elevating [Ca^2+]_i by uncaging Ca^2+ from nitrophenyl- (NP-EGTA) or by photoliberating inositol 1,4,5-trisphosphate (InsP_3) induced an ionic Current with biophysical properties similar to that elicited by cADPr. These results suggest that cADPr activates a Ca^2+ wave by releasing Ca^2+ from intracellular ryanodine receptors and that the rise in [Ca^2+]_i triggers a non-selective monovalent cation Current that does not seem to contribute to the global Ca^2+ elevation.
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Ca2+ signalling and Membrane Current activated by cADPr in starfish oocytes
Pflugers Archiv : European journal of physiology, 2003Co-Authors: Francesco Moccia, Gilda A. Nusco, Dmitri Lim, Emanuela Ercolano, Gianni Gragnaniello, Euan R. Brown, Luigia SantellaAbstract:Cyclic ADP-ribose (cADPr) is a second messenger that regulates intracellular free [Ca2+] ([Ca2+]i) in a variety of cell types, including immature oocytes from the starfish Astropecten auranciacus. In this study, we employed confocal laser scanning microscopy and voltage clamp techniques to investigate the source of the cADPr-elicited Ca2+ wave originating from the cortical Ca2+ patches we have described previously. The Ca2+ swing was accompanied by a Membrane Current with a reversal potential of ≈+20 mV. Decreasing external Na+ almost abolished the Current without affecting the Ca2+ response. Removal of extracellular Ca2+ altered neither the Ca2+ transient nor the ionic Current, nor did the holding potential exert any effect on the Ca2+ wave. Both the Ca2+ response and the Membrane Current were abolished when BAPTA, ruthenium red or 8-NH2-cADPr were preinjected into the oocytes, while perfusion with ADPr did not elicit any [Ca2+]i increase or ionic Current. However, elevating [Ca2+]i by uncaging Ca2+ from nitrophenyl- (NP-EGTA) or by photoliberating inositol 1,4,5-trisphosphate (InsP3) induced an ionic Current with biophysical properties similar to that elicited by cADPr. These results suggest that cADPr activates a Ca2+ wave by releasing Ca2+ from intracellular ryanodine receptors and that the rise in [Ca2+]i triggers a non-selective monovalent cation Current that does not seem to contribute to the global Ca2+ elevation.
Yoshio Watanabe - One of the best experts on this subject based on the ideXlab platform.
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Electrophysiological effects of amrinone on the automaticity and Membrane Current system of the rabbit sinoatrial node cells
Heart and Vessels, 1998Co-Authors: Tadayoshi Hata, Masao Nishimura, Kayo Ogino, Hirohide Uchiyama, Yoshio WatanabeAbstract:To elucidate the physiological role of phosphodiesterase (PDE) in cardiac pacemaker cells, we studied the electrophysiological effects of amrinone, an inhibitor of PDE type III, on the spontaneous action potential (AP) and Membrane Currents, using small preparations (0.2 × 0.2 × 0.1mm) of rabbit sinoatrial (SA) node cells. Amrinone (0.1–1.0mM) progressively increased the AP amplitude, maximal rate of depolarization, and spontaneous firing frequency, shortened the AP duration, and made the threshold potential more negative. In voltage-clamp experiments using double microelectrode techniques, 0.1mM amrinone increased the Ca^2+ Current ( I _Ca) obtained on step depolarization from −40 to −10mV by 25.86% ± 4.6% ( P < 0.05, n = 6), the delayed rectifier K^+ Current ( I _K) tail obtained on repolarization from 10 to −60mV by 22.8% ± 4.7% ( P < 0.05, n = 6), and the hyperpolarization-activated inward Current ( I _h) at −90mV by 19.5% ± 7.3% ( P < 0.05, n = 6), respectively. Amrinone did not affect the slope factors of either the inactivation curve for I _Ca ( f∞ curve) or the activation curve for the delayed rectifier I _K ( p∞ curve). These results suggest that this PDE III inhibitor exerts a positive chronotropic action by enhancing the availability and the conductance of all the tested Membrane Currents in rabbit SA node cells.
David A. Eisner - One of the best experts on this subject based on the ideXlab platform.
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the effect of tetracaine on stimulated contractions sarcoplasmic reticulum ca2 content and Membrane Current in isolated rat ventricular myocytes
The Journal of Physiology, 1998Co-Authors: C L Overend, S C Oneill, David A. EisnerAbstract:1The effects of tetracaine were examined on rat ventricular myocytes. In both field-stimulated and voltage-clamped cells tetracaine (100–200 μM) produced an initial decrease of contraction before a recovery towards the control level. Removal of tetracaine produced a transient overshoot of contraction to levels greater than the control. 2The transient decrease of contraction produced by tetracaine was accompanied by a small transient increase in the integral of the L-type Ca2+ Current and a larger transient decrease of the Na+-Ca2+ exchange Current on repolarization. These are attributed to decreased systolic release of Ca2+. On removal of tetracaine there was an increase of the Na+-Ca2+ exchange Current. Before the addition of tetracaine, calculated Ca2+ influx and efflux across the sarcolemma were approximately equal. On adding tetracaine, efflux was transiently less than influx and, on removal of tetracaine, efflux was greater than influx. 3These changes in Ca2+ fluxes result in an increase of cell Ca2+ during exposure to tetracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca2+ and integrating the resulting Na+-Ca2+ exchange Current. 4It is concluded that the effects of tetracaine can be accounted for by depression of calcium-induced Ca2+ release (CICR). The response is transient because the inhibition is compensated for by an increase of SR Ca2+ content such that there is no steady-state effect on the magnitude of the systolic Ca2+ transient. The consequences of this result for the effects of other modulators of CICR are discussed.
Helmut Kettenmann - One of the best experts on this subject based on the ideXlab platform.
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ATP-induced Membrane Currents in ameboid microglia acutely isolated from mouse brain slices
Neuroscience, 1996Co-Authors: Stefan A. Haas, J Brockhaus, Alexej Verkhratsky, Helmut KettenmannAbstract:Microglial cells were harvested from the surface of corpus callosum slices acutely isolated from the brain of neonatal (five- to seven-day-old) mice. TransMembrane ionic Currents were measured employing a standard whole-cell voltage-clamp technique. The extracellular application of 1 mM ATP triggered the generation of a complex Membrane Current comprising three components: (i) an initial fast inward Current which had a reversal potential at about -20 to -15 mV; (ii) this initial component was followed by a steady-state inward Current with reversal potential about -50 to -40 mV; and (iii) a delayed inward Current with a reversal potential close to 0 mV. The first two components (fast and steady-state) had an activation threshold at 10 microM ATP, and 100 microM ATP evoked an almost maximal response. In contrast, the third component of ATP-induced inward Membrane Current could be observed only while 1 mM ATP was applied. The increase in concentration of tetra-anionic form of ATP (ATP4-) by removal of divalent cations from the bath solution substantially lowered the activation threshold for the delayed component of ATP-induced Membrane Current; conversely, lowering the ATP4- concentration (by replacing Ca2+ with Mg2+) resulted in its disappearance. These results suggest that ATP4- acts as a true agonist for the activation of the delayed ATP-induced Membrane Current. We conclude that microglial cells express several purinoreceptor subtypes. The activation of these receptors might play a role in intracellular signal transduction in brain microglia.
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Heterogeneity in the Membrane Current pattern of identified glial cells in the hippocampal slice
The European journal of neuroscience, 1992Co-Authors: Christian Steinhäuser, T. Berger, Michael Frotscher, Helmut KettenmannAbstract:Glial cells, acutely isolated or in tissue culture, have previously been shown to express a variety of voltage-gated channels. To resolve the question whether such channels are also expressed by glial cells in their normal cellular environment, we have applied the patch-clamp technique to study glial cells in hippocampal slices of 10 - 12-day-old mice. Based on the Membrane Current pattern, we distinguished four glial cell types. One was characterized by passive, symmetrical K+ Currents activated in depolarizing and hyperpolarizing directions. A second population showed a similar Current pattern, but with a marked decay of the Current during the 50-ms voltage jumps. In a third population, the decaying passive Currents were superimposed with a delayed rectifier outward Current and, in some cases, with a slow inward Current activated by depolarization. The fourth population expressed delayed rectifying outward Currents, an inward rectifier K+ Current and fast inward Currents activated by depolarization. To unequivocally identify the glial cells we combined electrophysiological and ultrastructural characterizations. Therefore, cells were filled with the fluorescent dye lucifer yellow during characterization of their Membrane Currents, the fluorescence of the dye was used to convert diaminobenzidine to an electron-dense material, and subsequently slices were inspected in the electron microscope. Recordings were obtained from cells in the stratum radiatum and were identified as glial by their size, the characteristic chromatin distribution, and the lack of synaptic Membrane specializations.