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 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 (<i>cir /cir </i>) mice), an animal model for human deafness (DFNB6 type), was investigated using a whole cell patch clamp technique. Littermate heterozygous (+/<i>cir</i> ) and ICR mice of the same age (postnatal day (P) 0 &#8211;P6) were used as controls. Voltage steps from &#8211;100 mV to 40 mV elicited small inward currents (&#8211;100 mV~&#8211;70 mV) and slow rising K⁺ outward currents (&#8211;60 mV ~40 mV) which activated near &#8211;50 mV in all OHCs tested. Linopirdine, a known blocker of K⁺ currents activated at negative potentials (I _K,n), did cause inhibition at varying degree (severe, moderate, mild) in K⁺ outward currents of heterozygous (+<i>/cir</i> ) or homozygous (<i>cir /cir</i> ) 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 (+<i>/cir </i>) or homozygous (<i>cir /cir</i> ) mice OHCs were close to those reported in I_K,n, biophysical and pharmacological properties of K⁺ outward currents, such as the activation close to &#8211;50 mV, small inward currents evoked by hyperpolarizing steps and TEA sensitivity, were not in line with I _K,n reported in other tissues. Our results show that the delayed rectifier type K⁺ outward currents, which are not similar to I _K,n with respect to biophysical and pharmacological properties, are inhibited by linopirdine in the developing (P0~P6) homozygous (<i>cir /cir</i> ) or heterozygous (+<i>/cir </i>) mice OHCs.