• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.383-388
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• 2015

$K^+$ outward currents in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), were investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) mice of the same age (postnatal day (P) 0-P6) were used as controls. Similar slow rising $K^+$ currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different. The values of Vhalf for activation were significantly different in the heterozygous (+/cir) and homozygous (cir/cir) mice ($-8.1{\pm}2.2mV$, heterozygous (+/cir) mice (n=7) and $-17.2{\pm}4.2mV$, homozygous (cir/cir) mice (n=5)). The inactivation curve was expressed by a single first order Boltzmann equation in the homozygous (cir/cir) mice, while it was expressed by a sum of two first order Boltzmann equations in the heterozygous (+/cir) mice. The $K^+$ current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes. Removal of external $Ca^{2+}$ did not affect the $K^+$ currents in either genotype, indicating that the higher sensitivity of $K^+$ current to TEA in the homozygous (cir/cir) mice was not due to an early expression of $Ca^{2+}$ activated $K^+$ channels. Our results suggest that the $K^+$ outward current of developing homozygous (cir/cir) mice OHCs is different in both biophysical and pharmacological aspects than that of heterozygous (+/cir) mice.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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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.