Leukotriene C4 modulation of muscarinic K+ current activation in bullfrog atrial myocytes.
Leukotriene C4 modulation of muscarinic K+ current activation in bullfrog atrial myocytes.
复制标题
白三烯 C4 对牛蛙心房肌细胞中毒蕈碱 K 电流激活的调节。
DOI：
10.1085/jgp.102.1.125
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Breitwieser,GE
中科院分区：
文献类型：
--
作者：
Scherer,RW;Lo,CF;Breitwieser,GE
The effects of leukotriene C4 (LTC4) on activation of muscarinic acetylcholine receptor (mAChR)-stimulated, inwardly rectifying K+ current (I~ Achl) were examined in single bullfrog atrial myocytes using the whole-cell patch clamp technique. LTC4 produced a reversible, concentration-dependent increase in steady-state, guanosine--y-thiotriphosphate (GTP~ tS)-activated IKt^ Chl, with a K0. 5 of 3.1 IzM. LTC4 also increased the rate of GTP~/S-mediated IKIAChl activation, both in the absence and presence of 1 nM ACh, with comparable K0. 5 values of 4.7 izM under basal conditions and 4.9 IzM in the presence of 1 nM ACh. LTC4 did not alter the relative affinities of the G protein, Gk, for GTP~/S and GTP. We hypothesize that all of the effects of LTC4 on the kinetics of Gk-mediated IKtACh] activation are produced at a common site with a K0. 5 of 3-5 I~ M. The effects of LTC4 on IKtACh] activation are fully reversible in the presence of GTP, IS. Under physiological conditions (ie, intracellular GTP), 10 izM LTC4 increased the ACh-activated peak Ir4AChl. Inhibitors of cellular LTC4 production, including 5, 8, 11, 14-eicosatetraynoic acid, baicalein, cinnamyl-3, 47dihydroxy-a-cyanocinnamate, and a-pentyl-4-(2-quinolinylmethoxy)-benzene methanol, greatly attenuated ACh-dependent IrqAChl activation, preventing activation of peak, and producing a lower steady-state IKIAChl (when compared with the control response in the same cell). Addition of exogenous LTC4 was able to overcome the effects of LTC4 synthesis inhibitors, restoring both the peak and steady-state Iv4AChl responses. Although the mechanism of LTC4-mediated modulation of IKtACnl activation is not known, our results suggest that endogenously produced lipoxygenase metabolites of arachidonic acid, specifically LTC4, are involved in the physiological process of I~ lAChl activation.
