Niflumic acid hyperpolarizes smooth muscle cells via calcium-activated potassium channel in spiral modiolar artery of guinea pigs.
OBJECTIVE
The influence of niflumic acid (NFA), a Cl(-)channel antagonist, on the membrane potentials in smooth muscle cells (SMC) of the cochlear spiral modiolar artery (SMA) in guinea pigs was examined.


METHODS
The intracellular recording and whole-cell recording technique were used to record the NFA-induced response on the acutely-isolated SMA preparation.


RESULTS
The SMC had 2 stable but mutually convertible levels of resting potentials (RP), that is, one was near -45 mV and the other was approximately -75 mV, termed as low and high RP, respectively. The bath application of NFA could cause a hyperpolarization in all the low RP cells, but had little effect on high RP cells. The induced responses were concentration-dependent. Large concentrations of NFA (>or=100 micromol/L) often induced a shift of a low RP to high RP in cells with an initial RP at low level, and NFA (up to 100 micromol/L) had little effect on the membrane potentials of the high RP cells. However, when the high RP cells were depolarized to a level beyond -45 mV by barium and ouabain, NFA hyperpolarized these cells with the similar effect on those cells initially being the low RP. The NFA-induced response was almost completely blocked by charybdotoxin, iberiotoxin, tetraethylammonium, 1,2-bis(2- aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester, but not by 4-aminopyridine, barium, glipizide, apamin, ouabain, and CdCl2.


CONCLUSIONS
NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca2+-activated potassium channels.
Departmeng of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Li
L
Li
Ke-tao
KT
Ma
Lei
L
Zhao
Jun-qiang
JQ
Si
Zhong-shuang
ZS
Zhang
He
H
Zhu
Jing
J
Li
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects*; D001464:Barium / Q000494:pharmacology; D018118:Chloride Channels / Q000009:adverse effects; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009544:Niflumic Acid / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018118:Chloride Channels; D024681:Potassium Channels, Calcium-Activated; D001464:Barium; D009544:Niflumic Acid; D010042:Ouabain