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

The effects of quinidine, an antiarrhythmic alkaloid, on potassium-selective channels in enzymatically dissociated gastric smooth muscle cells from Rana pipiens and Bufo 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 greater than 100 pS. Applications of quinidine (100-600 microM) 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 current-voltage 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 microM and 209 microM 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 microM quinidine. However, a 15 pS potassium channel was not affected by quinidine but was reversibly blocked by tetraethylammonium. Quinidine (500 microM) was also observed to decrease the opening probability of a 40 pS potassium channel from Bufo marinus without affecting its channel amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)