Niflumic acid hyperpolarizes smooth muscle cells via calcium-activated potassium channel in spiral modiolar artery of guinea pigs

Abstract

Aim: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 (100 mol/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 μmol/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 CdCl"2.Conclusion: NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca2-activated potassium channels. © 2008 CPS and SIMM.