DOI QR코드

DOI QR Code

Characteristics of K+ Outward Currents in the Cochlear Outer Hair Cells of Circling Mice within the First Postnatal Week

  • Ahn, Ji Woong (Department of Physiology, College of Medicine, Dankook University) ;
  • Kang, Shin Wook (Department of Physiology, College of Medicine, Dankook University) ;
  • Ahn, Seung Cheol (Department of Physiology, College of Medicine, Dankook University)
  • Received : 2015.04.30
  • Accepted : 2015.06.08
  • Published : 2015.07.01

Abstract

$K^+$ 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.

Keywords

References

  1. Marcotti W, Johnson SL, Holley MC, Kros CJ. Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells. J Physiol. 2003;548:383-400. https://doi.org/10.1113/jphysiol.2002.034801
  2. Marcotti W, Geleoc GS, Lennan GW, Kros CJ. Transient expression of an inwardly rectifying potassium conductance in developing inner and outer hair cells along the mouse cochlea. Pflugers Arch. 1999;439:113-122. https://doi.org/10.1007/s004240051134
  3. Marcotti W, Kros CJ. Developmental expression of the potassium current IK,n contributes to maturation of mouse outer hair cells. J Physiol. 1999;520 Pt 3:653-660. https://doi.org/10.1111/j.1469-7793.1999.00653.x
  4. Kros CJ, Ruppersberg JP, Rusch A. Expression of a potassium current in inner hair cells during development of hearing in mice. Nature. 1998;394:281-284. https://doi.org/10.1038/28401
  5. Lee JW, Lee EJ, Hong SH, Chung WH, Lee HT, Lee TW, Lee JR, Kim HT, Suh JG, Kim TY, Ryoo ZY. Circling mouse: possible animal model for deafness. Comp Med. 2001;51:550-554.
  6. Chung WH, Kim KR, Cho YS, Cho DY, Woo JH, Ryoo ZY, Cho KI, Hong SH. Cochlear pathology of the circling mouse: a new mouse model of DFNB6. Acta Otolaryngol. 2007;127:244-251. https://doi.org/10.1080/00016480600827071
  7. Kharkovets T, Dedek K, Maier H, Schweizer M, Khimich D, Nouvian R, Vardanyan V, Leuwer R, Moser T, Jentsch TJ. Mice with altered KCNQ4 $K^+$ channels implicate sensory outer hair cells in human progressive deafness. EMBO J. 2006;25:642-652. https://doi.org/10.1038/sj.emboj.7600951
  8. Hong SH, Kim MJ, Ahn SC. Glutamatergic transmission is sustained at a later period of development of medial nucleus of the trapezoid body-lateral superior olive synapses in circling mice. J Neurosci. 2008;28:13003-13007. https://doi.org/10.1523/JNEUROSCI.3002-08.2008
  9. Helyer RJ, Kennedy HJ, Davies D, Holley MC, Kros CJ. Development of outward potassium currents in inner and outer hair cells from the embryonic mouse cochlea. Audiol Neurootol. 2005;10:22-34. https://doi.org/10.1159/000081545
  10. Mammano F, Ashmore JF. Differential expression of outer hair cell potassium currents in the isolated cochlea of the guinea-pig. J Physiol. 1996;496:639-646. https://doi.org/10.1113/jphysiol.1996.sp021715
  11. Liang GH, Jarlebark L, Ulfendahl M, Moore EJ. Mercury $Hg^{2+}$ suppression of potassium currents of outer hair cells. Neurotoxicol Teratol. 2003;25:349-359. https://doi.org/10.1016/S0892-0362(03)00008-4
  12. Marcotti W, Johnson SL, Kros CJ. A transiently expressed SK current sustains and modulates action potential activity in immature mouse inner hair cells. J Physiol. 2004;560:691-708. https://doi.org/10.1113/jphysiol.2004.072868
  13. Sah P. $Ca^{2+}$-activated $K^+$ currents in neurones: types, physiological roles and modulation. Trends Neurosci. 1996;19:150-154. https://doi.org/10.1016/S0166-2236(96)80026-9
  14. Marcotti W, Johnson SL, Kros CJ. Effects of intracellular stores and extracellular $Ca^{2+}$ on $Ca^{2+}$-activated $K^+$ currents in mature mouse inner hair cells. J Physiol. 2004;557:613-633. https://doi.org/10.1113/jphysiol.2003.060137