Inhibition of K outward currents by linopirdine in the cochlear outer hair cells of circling mice within the first postnatal week.

Inhibition of K outward currents by linopirdine in the outer hair cells (OHCs) of circling mice (homozygous (/) mice), an animal model for human deafness (DFNB6 type), was investigated using a whole cell patch clamp technique. Littermate heterozygous (+/) and ICR mice of the same age (postnatal day (P) 0 -P6) were used as controls. Voltage steps from -100 mV to 40 mV elicited small inward currents (-100 mV-70 mV) and slow rising K outward currents (-60 mV ~40 mV) which activated near -50 mV in all OHCs tested. Linopirdine, a known blocker of K currents activated at negative potentials (), did cause inhibition at varying degree (severe, moderate, mild) in K outward currents of heterozygous (+/) or homozygous (/) mice OHCs in the concentration range between 1 and 100 µM, while it was apparent only in one ICR mice OHC out of nine OHCs at 100 µM. Although the half inhibition concentrations in heterozygous (+/) or homozygous (/) mice OHCs were close to those reported in , biophysical and pharmacological properties of K outward currents, such as the activation close to -50 mV, small inward currents evoked by hyperpolarizing steps and TEA sensitivity, were not in line with reported in other tissues. Our results show that the delayed rectifier type K outward currents, which are not similar to with respect to biophysical and pharmacological properties, are inhibited by linopirdine in the developing (P0P6) homozygous (/) or heterozygous (+/) mice OHCs.