It is commonly accepted that the endocochlear DC potential (EP) of the cochlea is generated by electrogenic transport of potassium ion into the scala media from the marginal cells of the stria vascularis. In recent years, many models of the marginal cell have been developed in which the EP is generated by an electrogenic ion transport system localized in either the basal or apical membranes of the marginal cell. On the other hand, Salt et al. reported that EP cannot be generated by the marginal cells alone but, rather, may involve passive potassium movement across the apical membranes of basal cells. In this study, the effect of Nicorandil, a potassium channel opener, on EP and cochlear microphonics (CM) were investigated by perfusion through the perilymphatic space of the guinea pig from the scala tympani to the scala vestibuli with an artificial perilymph. The results of several concentrations were examined. Characteristic of Nicorandil, a vasodilatory agent, is an increase in membrane potassium conductance due to the opening of plasmalemma ATP-regulated K⁺ channels in cardiac muscle and vascular smooth muscle. This effect results from the membrane hyperpolarization and consequent reduced opening probability of voltage-dependent Ca²⁺ channels.
When the perilymphatic space was perfused with a solution containing 1×10^-4M Nicorandil, the EP level decreased from 74.8±2.4mV to+50.0±12.8mV and the CM amplitude fell to 78.6% of the control. At a concentration of 5×10^-4M, EP decreased from 77.8±4.1mV to 47.0±7.6mV and CM amplitude fell to 16.7%. At 1×10^-3M, EP decreased from 78.3±1.7mV to 8.8±5.4mV and CM fell to 28%. At all concentrations tested, CM gradually declined in parallel with the EP. In one out of four preparations, a decrease in EP produced by 1×10^-4M Nicorandil was reversed to the initial level after washout of Nicorandil by the control artificial endolymph perfusion. When the concentration of Nicorandil was 1×10^-3M or higher, interruption of perfusion did not bring about a recovery of EP but did stop any further decrease in the EP.
These results suggest that a reactive channel for Nicorandil, functioning as an ATP-regulated K⁺ channel opener, exists in the stria vascularis or the organ of Corti.