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Voltage‐dependence of Ca2+ agonist effect of YC‐170 on cardiac L‐type Ca2+ channels

1 We investigated the voltage‐dependence of the agonist actions of YC‐170, a dihydropyridine (DHP) derivative, on cardiac L‐type Ca2+ channels in rabbit ventricular cells, using the patch clamp technique. The characteristics of YC‐170 were compared with those of other DHP Ca2+ agonists (Bay K 8644, CGP 28392). Ca2+ channel activities were elicited by depolarizing pulses to 0 mV from a holding potential (HP) of either −80 mV or −40 mV. 2 YC‐170 (10 μM) increased Ca2+ channel activities when HP was set at −80 mV. However, decreasing HP to −40 mV abolished the agonist action. The agonist effect of Bay K 8644 (1 μM) on Ca2+ channels was elicited to the same extent at either HP. CGP 28392 (10 μm) also increased Ca2+ channel activities at both HPs, but its agonist effect was significantly larger at an HP of −80 mV than at −40 mV. 3 All of the three DHP Ca2+ agonists prolonged open times of Ca2+ channels, but the prolongation did not correspond to the voltage‐dependence of Ca2+ agonist effects of the three DHPs. 4 YC‐170 markedly reduced the closed time of the Ca2+ channel when the HP was at −80 mV, but prolonged it at HP of −40 mV. Bay K 8644 reduced closed times at an HP of −80 mV. At an HP of −40 mV, Bay K 8644 slightly reduced closed times. CGP 28392 reduced closed times at an HP of −80 mV and prolonged those at an HP of −40 mV. Thus the voltage‐dependence of the agonist effects of these agents was in good agreement with the voltage‐dependence of changes in closed times of Ca2+ channel. 5 Two mechanisms may be involved in the agonist action of YC‐170; a prolongation of open times, and a reduction of closed times of Ca2+ channels, i.e. an increase in reopening. The former mechanism is not dependent on HP and the latter mechanism is highly dependent on HP. Thus, the voltage‐dependence of the agonist action may be attributed to the voltage‐dependence of their enhancing effect on reopening of Ca2+ channels.