Niflumic acid hyperpolarizes the smooth muscle cells by opening BK(Ca) channels through ryanodine-sensitive Ca(2+) release in spiral modiolar artery.
The mechanism by which niflumic acid (NFA), a Cl(-) channel antagonist, hyperpolarizes the smooth muscle cells (SMCs) of cochlear spiral modiolar artery (SMA) was explored. Guinea pigs were used as subjects and perforated patch clamp and intracellular recording technique were used to observe NFA-induced response of SMC in the acutely isolated SMA preparation. The results showed that bath application of NFA, indanyloxyacetic acid 94 (IAA-94) and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) caused hyperpolarization and evoked outward currents in all cells at low resting potential (RP), but had no effects in cells at high RP. In the low RP SMCs, the average RP was about (-42.47+/-1.38) mV (n=24). Application of NFA (100 mumol/L), IAA-94 (10 mumol/L) and DIDS (200 mumol/L) shifted the RP to (13.7+/-4.3) mV (n=9, P<0.01), (11.4+/-4.2) mV (n=7, P<0.01) and (12.3+/-3.7) mV (n=8, P<0.01), respectively. These drug-induced responses were in a concentration-dependent manner. NFA-induced hyperpolarization and outward current were almost blocked by charybdotoxin (100 nmol/L), iberiotoxin (100 nmol/L), tetraethylammonium (10 mmol/L), BAPTA-AM (50 mumol/L), ryanodine (10 mumol/L) and caffeine (0.1-10 mmol/L), respectively, but not by nifedipine (100 mumol/L), CdCl2 (100 mumol/L) and Ca(2+)-free medium. It is concluded that NFA induces a release of intracellular calcium from the Ca(2+) stores and the released intracellular calcium in turn causes concentration-dependent and reversible hyperpolarization and evokes outward currents in the SMCs of the cochlear SMA via activation of the Ca(2+)-activated potassium channels.
Li
Li
L
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ma
Ke-Tao
KT
Zhao
Lei
L
Si
Jun-Qiang
JQ
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D003051:Cochlea / Q000098:blood supply; D006168:Guinea Pigs; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008564:Membrane Potentials; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D009544:Niflumic Acid / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D012433:Ryanodine; D009544:Niflumic Acid; D002118:Calcium