Inactivation of L-type calcium channels in cardiomyocytes. Experimental and theoretical approaches.
The L-type calcium current (ICa) plays an important role in excitation-contraction coupling of heart cells. It is critical for forming the major trigger for Ca(2+)-induced Ca(2+) release from the sarcoplasmic reticulum and hence its feedback regulation is of fundamental biological significance. The channel inactivation sharpens the kinetics and temporal precision of the Ca(2+) signals so that it prevents longer-term increases in free intracellular Ca(2+) concentration. Cardiac L-type Ca(2+) channels are known to inactivate through voltage- and Ca(2+)-dependent mechanisms. Pure voltage-dependent inactivation has a much slower time course of development than Ca(2+)-dependent inactivation and plays minor role in inhibition of Ca(2+) influx into the cell. The major determinant of the inactivation kinetics of Ca(2+) current during depolarization is Ca(2+)-dependent mechanisms. Furthermore, it is possible to distinguish two phases in Ca(2+)-dependent inactivation of calcium current: a slow phase that depends on Ca(2+) flow through the channels (Ca(2+) current-dependent inactivation) and a fast one that depends on Ca(2+) released from the sarcoplasmic reticulum (Ca(2+) release-dependent inactivation). Although both Ca(2+) released from the SR and Ca(2+) permeating channels play a role, SR-released Ca(2+) is the most effective inactivation mechanism in inhibition of Ca(2+) entry through the channel.
Kubalová
Z
Z
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia. umfgkuba@savba.sk
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D020746:Calcium Channels, L-Type; D002118:Calcium