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KMID : 0811720170210020251
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Korean Journal of Physiology & Pharmacology
2017 Volume.21 No. 2 p.251 ~ p.257
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Inhibition of K+ outward currents by linopirdine in the cochlear outer hair cells of circling mice within the first postnatal week
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Kang Shin-Wook
Ahn Ji-Woong
Ahn Seung-Cheol
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Abstract
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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 (I K,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 in I K,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 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 (cir /cir ) or heterozygous (+/cir ) mice OHCs.
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KEYWORD
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Circling mice, I K, n, K+ current, Linopirdine, Outer hair cell
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