The L-type Ca
2+ channel (Ca
V1.2) shows clear Ca
2+-dependent facilitation and inactivation. Here we have examined the effects of calmodulin (CaM) and Ca
2+ on Ca
2+ channel in guinea-pig ventricular myocytes in the inside-out patch mode, where rundown of the channels was controlled. At a free [Ca
2+] 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 [Ca
2+] <0.01
μM or with a Ca
2+-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 [Ca
2+]. A simple model for CaM- and Ca
2+-dependent modulations of the channel activity, which involves two CaM-binding sites, was proposed. We suggest that both apoCaM and Ca
2+/CaM can induce facilitation and inactivation of Ca
V1.2 Ca
2+ channels and that the basic role of Ca
2+ is to accelerate CaM-dependent facilitation and inactivation.
View full abstract