Voltage-gated outward K currents in frog saccular hair cells

A biophysical analysis of the voltage-gated K (K-v) currents of frog saccular hair cells enzymatically isolated with bacterial protease VIII was carried out, and their contribution to the cell electrical response was addressed by a modeling approach. Based on steady-state and kinetic properties of inactivation, two distinct K-v currents were found: a fast inactivating I-A and a delayed rectifier I-DRK. I-A exhibited a strongly hyperpolarized inactivation V-1/2 (-83 mV), a relatively rapid single exponential recovery from inactivation (tau(rec) of similar to100 ms at -100 mV), and fast activation and deactivation kinetics. I-DRK showed instead a less-hyperpolarized inactivation V-1/2 (-48 mV), a slower, double-exponential recovery from inactivation (tau(rec1) similar to 490 ms and tau(rec2) similar to 4,960 ms at -100 mV), and slower activation and deactivation kinetics. Steady- state activation gave a V-1/2 and a k of -46.2 and 8.2 mV for I-A and -48.3 and 4.2 mV for I-DRK. Both currents were not appreciably blocked by bath application of 10 mM TEA, but were inhibited by 4-AP, with I-DRK displaying a higher sensitivity. I-DRK also showed a relatively low affinity to linopirdine, being half blocked at similar to50 muM. Steady-state and kinetic properties of I-DRK and I-A were described by 2nd- and 3rd-order Hodgkin-Huxley models, respectively. The goodness of our quantitative description of the K-v currents was validated by including I-A and I-DRK in a theoretical model of saccular hair cell electrical activity and by comparing the simulated responses with those obtained experimentally. This thorough description of the I-DRK and I-A will contribute toward understanding the role of these currents in the electrical response on this preparation.