Abstract
Atrial myocytes express α1 subunits of the L-type Ca2+ channel, CaV1.2 and CaV1.3. CaV1.3 activates and inactivates at voltages lower than those of CaV1.2 by approximately -15mV. We have previously reported that the replacement of the 2nd transmembrane domain of CaV1.2 by that of CaV1.3 (CD2) mimicked the negative shift of the steady-state inactivation. In order to elucidate the gating regulatory mechanism of CaV1.3, we expressed CaV1.2, CaV1.3, or CaV1.2/CaV1.3 chimera in BHK6 cells and examined their kinetics. The voltage-dependent inactivation (VDI) kinetics of CaV1.3 was much slower than that of CaV1.2. On the other hand, VDI was accelerated in CD2. Interestingly, substitution of Ile/Tyr (CaV1.2-type) for Val/His (CaV1.3-type) in IIS4 of CD2 slowed the inactivation kinetics. The replacement of C-terminal region of CaV1.2 by that of CaV1.3 (CTD) slowed the VDI kinetics. These results indicate that : 1) the insertion of CaV1.3-derived Val/His in IIS4 (voltage sensor) into CaV1.2 somehow accelerates the inactivation, but not in CaV1.3, 2) C-terminal region of CaV1.3 plays an important role in the slow inactivation kinetics of CaV1.3. It has been reported in CaV1.3(-/-) mice that action potential (AP) duration of the sinus nodal cells was shorter than that of wt. Our results suggest that CaV1.3 continues to be activated during APs, and thus contributes to maintain AP duration in atrial myocytes. [J Physiol Sci. 2007;57 Suppl:S79]
