title: Inhibition of K+outward currents by linopirdine in the cochlear outer hair cells of circling mice within the first postnatal week.
abstract: Inhibition of K+outward currents by linopirdine in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), was investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) 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 (IK,n), did cause inhibition at varying degree (severe, moderate, mild) in K+outward currents of heterozygous (+/cir) or homozygous (cir/cir) 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 (+/cir) or homozygous (cir/cir) mice OHCs were close to those reported inIK,n, 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 withIK,nreported in other tissues. Our results show that the delayed rectifier type K+outward currents, which are not similar toIK,nwith respect to biophysical and pharmacological properties, are inhibited by linopirdine in the developing (P0~P6) homozygous (cir/cir) or heterozygous (+/cir) mice OHCs.
authors.affiliation: Department of Physiology, College of Medicine, Dankook University, Cheonan 31116, Korea.
authors.forename: Shin Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Physiology, College of Medicine, Dankook University, Cheonan 31116, Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Ahn
authors.affiliation: Department of Physiology, College of Medicine, Dankook University, Cheonan 31116, Korea.
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Ahn
keywords: Circling mice; IK,n; K+ current; Linopirdine; Outer hair cell