Vascular and cardiac ionic channels and drug specificity

1. 花生四烯酸（AA）在心脏和平滑肌细胞中对早期瞬态K （a型）电流的调节差异已在门静脉、精囊、输精管、结肠和胃底分离的平滑肌细胞中发现了sa型电流。a型电流型平滑肌细胞的激活和失活动力学以及对4-氨基吡啶的敏感性与心肌细胞相似，表明这两种肌肉中的通道属于同一家族。在去极化的早期阶段，电流在平滑肌细胞中的功能作用是抑制AP或延迟AP放电，因此，与心肌细胞中的功能作用不同。我们发现1muM AA的应用使这些平滑肌细胞的a型电流降低了约50%。而在兔心房肌细胞中，只有在高浓度AA （bbb30mum）作用下，a型电流才有明显的减少，说明AA诱导的a型电流减少在平滑肌细胞中的生理意义更大。aa诱导的a型电流还原不受环氧合酶、脂氧合酶和超氧化物歧化酶抑制剂的影响。蛋白激酶C抑制剂可部分减少这种减少。III类抗心律失常药物对延迟整流K电流调制的差异III类抗心律失常药物延长心肌细胞AP持续时间和不应期。虽然心肌细胞延迟整流K电流可被III类抗心律失常药物选择性抑制，但药物对平滑肌延迟整流K电流的影响尚不明确。猪冠状动脉平滑肌细胞延迟整流K电流对E-4031、MS-551等III类抗心律失常药物的敏感性较低，但对奎尼丁的敏感性相当。III类抗心律失常药物对心脏延迟整流K电流的选择性优于血管平滑肌，特别是冠状动脉的选择性，这是非常重要的，因为抑制延迟整流K电流可增加平滑肌的膜兴奋性和收缩性。季铵盐对平滑肌钙敏感性的影响。为了研究肌醇1,4,5三磷酸（IP_3）对心肌细胞和平滑肌细胞钙动员的影响，研究了一种推测的K通道阻滞剂与IP_3对肌浆网钙释放的作用。出乎意料的是，四己基溴化铵作为中枢神经系统内质网中一种有效的K通道阻滞剂，通过不同的机制显著增加了β -叶磷脂皮敷的平滑肌条的Ca敏感性。钙敏感性增加的机制既不包括肌球蛋白轻链激酶活性的增加，也不包括肌球蛋白去磷酸酶活性的降低。少

1. Differences in regulation of early transient K (A-type) currents by arachidonic acid (AA) in cardiac and smooth muscle cellsA-type currents have been identified in smooth muscle cells isolated from portal vein, seminal vesicle, vas deferens, colon and stomach fundus. The activation and inactivation kinetics and the sensitivity to 4-aminopyridine of A-type current sin smooth muscle cells are similar to those in cardiac muscle cells, suggesting the same family of the channels in these muscles. The functional roles of the current in smooth muscle cells are suppressing AP or making a delay for AP firing during the early stage of depolarization and are, therefore, different from those in cardiac myocytes. We found that the application of 1muM AA reduced A-type current by about 50 % in these smooth muscle cells. In contract, substantial reduction of A-type current was observed in rabbit atrial myocytes only when much higher concentration of AA (>30muM) was applied, implying that physiolog … More ical significance of AA-induced reduction of A-type current is larger in smooth muscle cells. The AA-induced reduction of A-type current was not affected by inhibitors of cyclooxy-genase, lipoxygenase or superoxide dismutase. The reduction was partly decreased by proteinkinase C inhibitior.2. Differences in modulation of delayed rectifier K current by Class III antiarrythmic drugsClass III antiarrythmic drug prolongs AP duration and refractory period in cardiac myocytes. Although delayed rectifier K current is selectively suppressed by Class III anitiarrythmic drugs in cardiac myocytes, effects of the drugs on delayed rectifier K current in smooth muscle have not been clarified yet. The delayed rectifier K current in smooth muscle cells of the porcine coronary artery was much less sensitive to Class III antiarrythmic drugs, such as E-4031 and MS-551 but was equally sensitive to quinidine. The selectivity of Class III antiarrythmic drugs to cardiac delayed rectifier K current over that in vascular smooth muscle, especially that of coronary artery is quite important because suppression of delayed rectifier K current increases membrane excitability and contractility of the smooth muscle.3. Increase in Ca sensitivity in smooth muscle by quaternary ammonium salt.To examine the difference in Ca mobilization in cardiac and smooth muscle cells by inositol 1,4,5 trisphosphate (IP_3), effects of a putative blocker of K channels which couple with Ca release from sarcoplasmic reticulum by IP_3 were examined. Unexpectedly, tetrahexylammonium bromide, which has been reported as a potent K channel blocker in endoplasmic reticulum of central nervous system, markedly increased Ca sensitivity of smooth muscle strip skinned by beta-escin by separate mechanism. The mechanism underlying the increase in Ca sensitivity includes neither an increase in myosin light chain kinase activity nor a decrease in myosin dephosphatase activity. Less