Acta Pharmacologica Sinica 2008 July; 29 (7): 789-799; doi: 10.1111/j.1745-7254.2008.00803.x

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 μmol/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 CdCl₂.

Conclusion: NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca²⁺-activated potassium channels.

Keywords: spiral modiolar artery; smooth muscle cells; niflumic acid; hyperpolarization; Ca²⁺-activated potassium channels; cochlea