抄録
Voltage-gated L-type Ca2+ channel current (ICa) can be enhanced by preceding strong depolarization. Although this phenomenon is well recognized as voltage-dependent facilitation, its fundamental mechanisms are still unknown. Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been reported to play a key role in this process. Therefore we aimed to further clarify these regulation using the whole-cell mode of patch-clamp technique in HEK 293 cells expressing CaV1.2b, β2 and CaMKII. Voltage-dependent facilitation was Ca2+-dependent, and was prevented by CaMKII-inhibitor KN93 and autocamtide-2-related inhibitory peptide. Sixteen putative phosphorylation sites in CaV1.2b and β2 subunits according to the consensus sequences which were previously reported. CaV1.2b subunit truncated at amino acid 1728 did not affect voltage-dependent facilitation of ICa. Replacement of Ser1512 and/or Ser1570 in CaV1.2b subunit by Ala markedly attenuated the voltage-dependent facilitation of ICa, while other mutants had no effects. These results indicate that voltage-dependent facilitation of ICa is CaMKII-dependent and is generated by phosphorylation of CaV1.2b at Ser1512 and/or Ser1570. [J Physiol Sci. 2007;57 Suppl:S233]
