A NOVEL ACTION OF QUININE AND QUINIDINE ON THE MEMBRANE CONDUCTANCE OF NEURONS FROM THE VERTEBRATE RETINA

The cinchona alkaloids quinine and quinidine have been shown to block a broad range of voltage-gated membrane conductances in a variety of e xcitable tissues. Using the whole-cell version of the patch damp techn ique, we examined the effects of these compounds on voltage-dependent currents from horizontal cells dissociated enzymatically from the all- rod retina of the skate. We report here a novel and unexpected action of quinine and quinidine on isolated horizontal cells. In addition to blocking several of the voltage-activated currents of these cells, the introduction of the alkaloids evoked a large outward current when the cells were held at depolarized potentials. Using tail current analysi s, the reversal potential of the outward current was close to O mV, an d the current was markedly suppressed by extracellularly applied cobal t, acetate, and halothane. Depolarization in the presence of quinine a lso permitted entry into the cells of extracellularly applied Lucifer yellow (MW = 443 D), whereas a 3-kD fluorescein-dextran complex was ex cluded. These findings suggest that the large, apparently nonselective conductance induced by quinine and quinidine results from the opening of hemi-gap junctional channels.