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

作　　者：Li LI Ke-tao MA Lei ZHAO Jun-qiang SI Zhong-shuang ZHANG He ZHU Jing LI 

机构地区：[1]Departmeng of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China [2]Labo- ratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University Medical College, Xinjiang 832002, China [3]Fundamental Medical School of Wuhan University, Wuhan 430071, China

出　　处：《Acta Pharmacologica Sinica》2008年第7期789-799,共11页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China （No 30460043）; the Scientific and Technological Program for Overseas Personnel, the Ministry of Personnel, China （2006）; and the Key Program of Scientific and Technological Research, the Ministry of Education. China （Local Universities; No_ 207134）.

摘　　要：Aim： The influence of niflumic acid （NFA）, a C^1- 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 CdC12. Conclusion： NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca^2＋-activated potassium channels.Aim： The influence of niflumic acid （NFA）, a C^1- 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 CdC12. Conclusion： NFA induces a concentration-dependent reversible hyperpolarization in SMC in the cochlear SMA via activation of the Ca^2＋-activated potassium channels.

关 键 词：spiral modiolar artery smooth muscle cells niflumic acid HYPERPOLARIZATION Ca^2＋-activated potassium channels COCHLEA 

分 类 号：R4[医药卫生—临床医学]