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PKC-Independent Stimulation of Cardiac Na+/Ca2+ Exchanger by Staurosporine

机译:星形孢菌素对PKC非依赖性的心脏Na + / Ca2 +交换子的刺激

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[Ca2+]i transients by reverse mode of cardiac Na+/Ca2+ exchanger (NCX1) were recorded in fura-2 loaded BHK cells with stable expression of NCX1. Repeated stimulation of reverse NCX1 produced a long-lasting decrease of Ca2+ transients ('rundown'). Rundown of NCX1 was independent of membrane PIP2 depletion. Although the activation of protein kinase C (PKC) was observed during the Ca2+ transients, neither a selective PKC inhibitor (calphostin C) nor a PKC activator (PMA) changed the degrees of rundown. By comparison, a non-specific PKC inhibitor, staurosporine (STS), reversed rundown in a dose-dependent and reversible manner. The action of STS was unaffected by pretreatment of the cells with calphostin C, PMA, or forskolin. Taken together, the results suggest that the stimulation of reverse NCX1 by STS is independent of PKC and/or PKA inhibition.
机译:[Ca 2 + ] i 瞬态通过心脏Na + / Ca 2 + 交换器(NCX1)的反向模式进行记录在呋喃2加载的BHK细胞中,它们稳定表达NCX1。反向NCX1的反复刺激产生了Ca 2 + 瞬态的持久减少(“减少”)。 NCX1的减少与膜PIP 2 的消耗无关。尽管在Ca 2 + 瞬变过程中观察到了蛋白激酶C(PKC)的激活,但是选择性PKC抑制剂(calphostin C)和PKC激活剂(PMA)均未改变流失程度。相比之下,非特异性PKC抑制剂星形孢菌素(STS)以剂量依赖和可逆的方式逆转了衰变。用钙磷蛋白C,PMA或毛喉素对细胞进行预处理不会影响STS的作用。两者合计,结果表明STS对反向NCX1的刺激与PKC和/或PKA抑制无关。

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