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

• Published in: The Korean journal of physiology & pharmacology Vol. 21; no. 2; pp. 251 - 257
• Main Authors: Kang, Shin Wook, Ahn, Ji Woong, Ahn, Seung Cheol
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Physiological Society and The Korean Society of Pharmacology 01.03.2017; 대한약리학회
• Subjects: Original; 약리학; K+ current; Linopirdine; IK,n; Outer hair cell; Circling mice
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2017.21.2.251

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 (P0~P6) homozygous ( / ) or heterozygous (+/ ) mice OHCs.