A mechanism distinct from the L-type Ca current or Na-Ca exchange contributes to Ca entry in rat ventricular myocytes.
The aim of this paper was to characterize the pathways that allow Ca(2+) ions to enter the cell at rest. Under control conditions depolarization produced an increase of intracellular Ca concentration ([Ca(2+)](i)) that increased with depolarization up to about 0 mV and then declined. During prolonged depolarization the increase of [Ca(2+)](i) decayed. This increase of [Ca(2+)](i) was inhibited by nifedipine and the calculated rate of entry of Ca increased on depolarization and then declined with a similar time course to the inactivation of the L-type Ca current. We conclude that this component of change of [Ca(2+)](i) is due to the L-type Ca current. If intracellular Na was elevated then only part of the change of [Ca(2+)](i) was inhibited by nifedipine. The nifedipine-insensitive component increased monotonically with depolarization and showed no relaxation on prolonged depolarization. This component appears to result from Na-Ca exchange (NCX). When the L-type current and NCX were both inhibited (nifedipine and Na-free solution) then depolarization decreased and hyperpolarization increased [Ca(2+)](i). These changes of [Ca(2+)](i) were unaffected by modifiers of B-type Ca channels such as chlorpromazine and AlF(3) but were abolished by gadolinium ions. We conclude that, in addition to L-type Ca channels and NCX, there is another pathway for entry of Ca(2+) into the ventricular myocyte but this is distinct from the previously reported B-type channel.
Unit of Cardiac Physiology, University of Manchester, 3.18 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
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P
Kupittayanant
A W
AW
Trafford
M E
ME
Díaz
D A
DA
Eisner
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling; D006352:Heart Ventricles / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D012508:Sarcolemma / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D002118:Calcium