Abstract
Patch-clamp methods were developed to investigate the ion channel of the cellular membrane. The methods and modes of patch-clamp study and the physiological role of various ion channels have been briefly described in the literature. Patch-clamp methods have been used to study with isolated outer hair cells of the guinea pig cochlea, and various channels, such as voltage-dependent channels, mechano-electrical transduction channels and chemo-receptor channels, have been investigated. In this study, the effect of nicorandil, an ATP-regulated potassium channel opener, on isolated outer hair cells of the guinea pig cochlea were investigated using patch-clamp techniques in a conventional whole-cell mode. A characteristic effect of nicorandil is an increase in membrane potassium conductance due to opening of the plasmalemma ATP-regulated potassium channel in cardiac muscle and vascular smooth muscle. This effect results from membrane hyperpolarization and a consequent reduction in the probability of voltage-dependent calcium channel opening.
Application of nicorandil with 2 mM ATP concentration in a pipette ([ATP]i) activated an outward current in a concentration-dependent manner. Both an increase in [ATP]i to 10 mM and a decrease in [ATP]i to 0 mM inhibited this reaction. This outward current was reversed to the initial current after wash-out of nicorandil by application of the control artificial external solution. Tetraethylammonium inhibited the nicorandil-activated outward current. These results suggest that the nicorandil-activated outward current was an ATP-regulated potassium current, and that an ATP-regulated potassium channel exists in the membrane of the outer hair cells of the guinea pig cochlea.
