[Feature of ACh-sensitive potassium current in outer hair cells of guinea pig cochlea].
OBJECTIVE
To explore the feature of the ACh-sensitive potassium current in guinea pig cochlear outer hair cells.


METHODS
Cochlear outer hair cells of guinea pigs (n=38) were isolated by collagenase type IV. Under the whole-cell patch mode, the ions nature and the pharmacological properties of the ACh-sensitive potassium current were investigated by applying the inhibitors of calcium-dependent potassium currents and the inhibitors of nicotinic ACh receptor.


RESULTS
Following application of ACh, cochlear outer hair cells displayed a rapidly activating outward potassium current with a fast desensitized kinetic and a reversal (x +/- s) potential of (-67.3 +/- 8.2) mV (n=10). At the holding potential of -50 mV, the current amplitude of ACh-sensitive potassium current activated by 100 micronmol/L ACh was (506.6 +/- 186.3) pA (n=9). ACh-sensitive potassium current was sensitive to TEA (tetraethylammonium chloride, 10 mmol/L) and potently inhibited by the small conductance calcium-dependent potassium current (SK) blocker, apamin (1 micromol/L). Iberiotoxin (IBTX), the well-known blocker of big conductance calcium-dependent potassium current (BK), failed to inhibit the amplitude of the ACh-sensitive potassium current at the dose of 200 nmol/L. The dose for half-maximal response (EC50) of the ACh-sensitive potassium current was (33.5 +/- 5.7) micromol/L (n=7). The ACh-sensitive potassium current was sensitive to the GABA (gamma-aminobutyric acid)-A receptor blocker, bicuculline, and strongly inhibited by the selective blocker of the alpha 9-nicotinic ACh receptor, strychnine. Strychnine and bicuculline showed the dose-dependent blocking effect with a half inhibition-maximal response (IC50) of (22.3 +/- 2.6) nmol/L (n=7) and (1.2 +/- 0.4) micromol/L (n=6), respectively.


CONCLUSIONS
This work provides direct evidences that the ACh-sensitive SK current was present on guinea pig cochlear outer hair cells. The activation of the ACh-sensitive SK current was most possibly mediated by a alpha 9-nicotinic ACh receptor.
Guo
Chang-kai
CK
Department of Otorhinolaryngology, Union Hospital, Tongii Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Kong
Wei-jia
WJ
Yu
Qing-song
QS
Li
Guan-qiao
GQ
Li
Jia-li
JL
Li
Qing-tian
QT
D000818:Animals; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*
D015221:Potassium Channels; D011950:Receptors, Cholinergic; D011188:Potassium