Quinidine blockade of calcium-activated potassium channels in dissociated gastric smooth muscle cells

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Abstract
The effects of quinidine, an antiarrhythmic alkaloid, on potassium-selective channels in enzymatically dissociated gastric smooth muscle cells fromRana pipiens andBufo marinus were investigated using excised patches and the patch-clamp technique. The predominant potassium channel in these cells is the calcium- and voltage-activated maxi-K channel with a single-channel conductance > 100 pS. Applications of quinidine (100–600 μM) resulted in resolvable rapid flickerings between the open and blocked states with a corresponding reduction in open channel amplitude and an increase in open channel noise. The currentvoltage curves in the presence of internal quinidine and symmetrical potassium gradients displayed inward rectification. The time-constant of open-time distributions was found to decrease with increasing quinidine concentrations and membrane depolarization. The power-density spectrum of the channel current noise induced by internal quinidine showed a second Lorentzian component with a corner frequency larger than 300 Hz, suggesting that the noise is caused by rapid fluctuations between the open and blocked states. Apparent dissociation constants of 253 μM and 209 μM for membrane potentials of +20 mV and −60 mV, respectively, were obtained for the quinidine-induced blockade of Ca2+-activated K+ channels in these smooth muscle cells. Another potassium-selective channel with a single-channel conductance of 40 pS was completely blocked in the presence of 100 μM qunidine. However, a 15 pS potassium channel was not affected by quinidine but was reversibly blocked by tetraethylammonium. Quinidine (500 μM) was also observed to decrease the opening probability of a 40 pS potassium channel fromBufo marinus without affecting its channel amplitude. Thus, quinidine appears to have diverse mechanisms of action on potassium-selective channels in smooth muscle cells, ranging from totally ineffective to highly selective, as a slow blocker for some channels and as intermediate and fast blockers for others.