Slow voltage-dependent inactivation of L-type calcium channel Ca_V1.3 plays an important role in keeping its availability during pacemaker action potential.

Abstract

Atrial myocytes express L-type calcium channel α₁ subunits, Ca_V1.2 and Ca_V1.3. Ca_V1.3 activates and inactivates at voltages lower than those of Ca_V1.2 by approximately -17mV. We have previously reported that Ca_V1.3 shows slow voltage-dependent inactivation as compared to Ca_V1.2 and that the carboxy(C)-terminal region of Ca_V1.3 plays an important role in its slow inactivation kinetics. To elucidate the contribution of Ca_V1.3 currents in pacemaker potential, we examined ion current kinetics of Ca_V1.3, Ca_V1.2 and the chimeric channel CTD in which the C-terminal region of Ca_V1.2 was replaced by that of Ca_V1.3 by use of heterologous expression system. The recovery from the inactivation of Ca_V1.3 was significantly faster than those of Ca_V1.2 and CTD. The Ca_V1.3 channel current increased at both diastolic depolarization and repolarization during an action potential (AP). Under repetitive AP clamping with AP waveform of rabbit sino-atrial node at 1Hz, Ca²⁺ current and Ba²⁺ current through the three Ca²⁺ channels were gradually decreased and reached plateau. Interestingly, the availability of Ca_V1.3 was kept at higher level than that of Ca_V1.2. The amount of charge influx through Ca_V1.3 during an AP turned out to be larger than that of Ca_V1.2. Those results suggest that the unique voltage-dependent kinetics of Ca_V1.3 increase its contribution in Ca²⁺ influx and in keeping AP duration. [J Physiol Sci. 2008;58 Suppl:S58]