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 μM 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&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&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.