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Control of L‐type calcium current during the action potential of guinea‐pig ventricular myocytes
Author(s) -
Linz Klaus W.,
Meyer Rainer
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.425bb.x
Subject(s) - bapta , chemistry , biophysics , repolarization , egta , cardiac action potential , ventricular action potential , calcium , membrane potential , electrophysiology , patch clamp , myocyte , voltage dependent calcium channel , intracellular , endocrinology , biochemistry , medicine , biology , receptor , organic chemistry
1 During an action potential the L‐type Ca 2+ current ( I Ca,L ) activates rapidly, then partially declines leading to a sustained inward current during the plateau phase. The reason for the sustained part of I Ca,L has been investigated here. 2 In the present study the mechanisms controlling the I Ca,L during an action potential were investigated quantitatively in isolated guinea‐pig ventricular myocytes by whole‐cell patch clamp. To measure the actual time courses of I Ca,L and the corresponding L‐type channel inactivation ( f AP ) during an action potential, action potential‐clamp protocols combined with square pulses were applied. 3 Within the first 10 ms of the action potential the I Ca,L rapidly inactivated by about 50 %; during the plateau phase inactivation proceeded to 95 %. Later, during repolarization, the L‐type channels recovered up to 25 %. 4 The voltage‐dependent component of inactivation during an action potential was determined from measurements of L‐type current carried by monovalent cations. This component of inactivation proceeded rather slowly and contributed only a little to f AP . I Ca,L during an action potential is thus mainly controlled by Ca 2+ ‐dependent inactivation. 5 In order to investigate the source of the Ca 2+ controlling f AP , internal Ca 2+ homeostasis was manipulated by the use of Ca 2+ buffers (EGTA, BAPTA), by blocking Na + −Ca 2+ exchange, or by blocking Ca 2+ release from the sarcoplasmic reticulum (SR). Internal BAPTA markedly reduced the L‐type channel inactivation during the entire action potential, whereas EGTA affected f AP only during the middle and late plateau phases. Inhibition of Na + −Ca 2+ exchange markedly increased inactivation of L‐type channels. Although blocking SR Ca 2+ release decreased the fura‐2‐measured cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ) transient by about 90 %, it reduced L‐type channel inactivation only during the initial 50 ms of the action potential. Thus, it is Ca 2+ entering the cell through the L‐type channels that controls the inactivation process for the majority of the action potential. Nevertheless, SR Ca 2+ ‐release contributes 40–50 % to L‐type channel inactivation during the initial period of the action potential. However, the maximum extent of inactivation reached during the plateau is independent of Ca 2+ released from the SR. 6 For the first time, the actual time course of L‐type channel inactivation has been directly determined during an action potential under various defined [Ca 2+ ] i conditions. Thereby, the relative contribution to I Ca,L inactivation of voltage, Ca 2+ entering through L‐type channels, and Ca 2+ being released from the SR could be directly demonstrated.