Calmodulin- and Ca2+ -dependent facilitation and inactivation of the Cav1.2 Ca2+ channels in guinea-pig ventricular myocytes

The l-type ca2+ channel (cav1.2) shows clear ca2+-dependent facilitation and inactivation. here we have examined the effects of calmodulin (cam) and ca2+ on ca2+ channel in guinea-pig ventricular myocytes in the inside-out patch mode,where rundown of the channels was controlled. at a free [ca2+] of 0.1 μm,cam (0.15,0.7,1.4,2.1,3.5,and 7.0 μm) + atp (2.4 mm) induced channel activities of 27%,98%,142%,222%,65%,and 20% relative to the control activity,respectively,showing a bell-shaped relationship. similar results were observed at a free [ca2+] <0.01 μm or with a ca2+ -insensitive mutant,cam 1234,suggesting that apocam may induce facilitation and inactivation of the channel activity. the bell-shaped curve of cam was shifted to the lower concentration side with increasing [ca2+]. a simple model for cam-and ca2+ -dependent modulations of the channel activity,which involves two cam-binding sites,was proposed. we suggest that both apocam and ca2+/cam can induce facilitation and inactivation of cav1.2 ca2+ channels and that the basic role of ca2+ is to accelerate cam-dependent facilitation and inactivation. © 2010 the japanese pharmacological society.