Contribution of capacitative and non-capacitative Ca2+-entry to M3-receptor-mediated contraction of porcine coronary smooth muscle.

We studied the contribution of store-operated or capacitative Ca2+-entry (SOCE or CCE, respectively) through store-operated Ca2+ channels (SOCCs) and the contribution of Ca2+-entry through receptor-operated, non-selective cation channels (ROCCs or NSCCs, respectively), on the M3-receptor-mediated (270 nM Ach) contractile response of porcine coronary smooth muscle strips by means of the respective inhibitors. In the presence of L-VOCC blockade (1 microM verapamil), LOE 908 (inhibition of NSCCs) decreased the contractile response to 75+/-5% (p<0.01, n=6), 2-APB (inhibition of SOCCs) and SK and F 96365 (inhibition of SOCCs and of NSCCs) decreased the response to 45+/-4% (p<0.001, n=10) and to 23+/-2% (p<0.001, n=5), respectively (control: Ach response in the presence of verapamil alone). In the absence of L-VOCC blockade, LOE 908 reduced the Ach-response to 49+/-7% (p<0.001, n=8) and SK and F 96365 to 3+/-2% (p<0.001, n=4) of control, whereas 2-APB transiently increased the response (peak effect: 130+/-11%; p<0.05, n=8). We conclude: (1) the main source of activator Ca2+ during the M3-receptor-mediated contractile response is the Ca2+ influx through L-VOCCs; (2) however, in the presence of L-VOCC blockade, the contractile response is mainly due to Ca2+-entry through SOCCs; (3) NSCCs may be considerably involved in M3-receptor-mediated contraction as they may serve to depolarize the membrane potential and, thus, to open L-VOCCs; (4) in primary tissue of vascular smooth muscle, both, SOCE and Ca2+-entry through NSCCs are activated during M3-receptor stimulation.