Activation of PKC increases Na+-K+ pump current in ventricular myocytes from guinea pig heart.
Activation of PKC increases Na+-K+ pump current in ventricular myocytes from guinea pig heart.
复制标题
PKC 的激活增加了豚鼠心脏心室肌细胞中的 Na -K 泵电流。
DOI：
10.1007/s004240050828
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Baldo,GJ
中科院分区：
文献类型：
--
作者：
Gao,J;Mathias,RT;Cohen,IS;Wang,Y;Sun,X;Baldo,GJ
我们之前已经证明，α1-肾上腺素能受体的激活会增加豚鼠心室肌细胞中的 Na+-K+ 泵电流 (Ip)，并且这种增加可以被磷酸激酶 C (PKC) 阻滞剂消除。在这项研究中，我们检查了 PKC 激活剂对 Ip 的影响。佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 是一种 PKC 激活剂，可增加每个测试电位的 I，而不会改变其电压依赖性。半最大响应 (K0.5) 所需的浓度在 15 nM 胞质 [Ca2+] ([Ca2+]i) 下为 6 µM，在 314 nM [Ca2+]i 下为 13 nM。 [Ca2+]i 的最大增加约为 30%。另一种 PKC 激活剂 1,2-二辛酰基-sn-甘油 (diC8) 也有类似的增加。 PMA 对 IP 的影响被 PKC 抑制剂星形孢菌素消除，但不能被肽 PKI（一种蛋白激酶 A (PKA) 抑制剂）消除。 PMA 和 α1-肾上腺素能激动剂作用均对 [Ca2+]i 敏感，可被 PKC 抑制剂阻断，不受 PKA 抑制的影响，并且在所有电压下均均匀增加。然而，它们的不同之处在于，与 PMA 相比，α1 激活导致的最大增加为 15%，而通过 PMA 则为 30%，并且 α1 效应对 [Ca2+]i 的敏感度低于 PMA 效应。这些结果证明PKC的激活导致豚鼠心室肌细胞Ipin增加。此外，他们认为α1-肾上腺素能激活与Ipi的偶联完全是通过PKC进行的，然而α1-激活可能与特定的PKC群体偶联，而PMA是一种更全面的激动剂。
We have previously shown activation of α1-adrenergic receptors increases Na+-K+pump current (Ip) in guinea pig ventricular myocytes, and the increase is eliminated by blockers of phosphokinase C (PKC). In this study we examined the effect of activators of PKC onIp. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, increasedIPat each test potential without shifting its voltage dependence. The concentration required for a half-maximal response (K0.5) was 6 µM at 15 nM cytosolic [Ca2+] ([Ca2+]i) and13 nM at 314 nM [Ca2+]i. The maximal increase at either [Ca2+]iwas about 30%. Another activator of PKC, 1,2-dioctanoyl-sn-glycerol (diC8), increasedIpsimilarly. The effect of PMA onIPwas eliminated by the PKC inhibitor staurosporine, but not by the peptide PKI, an inhibitor of protein kinase A (PKA). PMA and α1-adrenergic agonist effects both were sensitive to [Ca2+]i, blocked by PKC inhibitors, unaffected by PKA inhibition, and increasedIpuniformly at all voltages. However, they differed in that α1-activation caused a maximum increase of 15% vs 30% via PMA, and α1-effects were less sensitive to [Ca2+]ithan PMA effects. These results demonstrate that activation of PKC causes an increase inIpin guinea pig ventricular myocytes. Moreover, they suggest that the coupling of α1-adrenergic activation toIpis entirely through PKC, however α1-activation may be coupled to a specific population of PKC whereas PMA is a more global agonist.