• Title/Summary/Keyword: Linopirdine

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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

  • Kang, Shin Wook;Ahn, Ji Woong;Ahn, Seung Cheol
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.251-257
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    • 2017
  • 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 $100{\mu}m$, while it was apparent only in one ICR mice OHC out of nine OHCs at $100{\mu}m$. 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.