Niflumic acid hyperpolarizes smooth muscle cells via calcium-activated potassium channel in spiral modiolar artery of guinea pigs1

Abstract

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. The intracellular recording and whole-cell recording technique were used to record the NFA-induced response on the acutely-isolated SMA preparation. 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. NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca2+-activated potassium channels.