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冈田酸增强非洲爪蟾卵母细胞中心脏α1亚基的预脉冲易化作用,但不增强内源性钙通道电流。

Okadaic acid enhances prepulse facilitation of cardiac alpha 1-subunit but not endogenous calcium channel currents in Xenopus laevis oocytes.

作者信息

Chahine M, Bibikova A, Sculptoreanu A

机构信息

Laval Hospital, Research Center, St-Foy, QC, Canada.

出版信息

Can J Physiol Pharmacol. 1996 Oct;74(10):1149-56.

PMID:9022835
Abstract

Xenopus laevis oocytes can be selected to express relatively high levels of endogenous Ca currents. These currents are facilitated by prepulses. Facilitated endogenous Ca currents are unaffected by okadaic acid, RpcAMPS or the dihydropyridine (DHP) antagonist (+) PN 200-110. The endogenous currents and facilitation of endogenous currents by depolarizing prepulses are fully blocked by 1 mM Cd2+. In contrast, oocytes injected with mRNA encoding for the rabbit cardiac alpha 1-subunit express prepulse-facilitated Ca channel currents that are highly enhanced by the phosphoprotein phosphatase inhibitor okadaic acid (3-fold) and blocked by RpcAMPS and the DHP antagonist (+) PN 200-110. While okadaic acid selectively stimulates prepulse facilitation of cardiac alpha 1-subunit Ca currents, the DHP agonist (+) SDZ 202-791 largely increases (5-fold) both the control (before prepulse) and facilitated currents (after prepulse). (+) SDZ 202-791 did not prevent the effect of RpcAMPS or okadaic acid on facilitation of cardiac alpha 1-subunit, suggesting that DHP stimulation is independent of phosphorylation leading to channel facilitation. The enhancement of prepulse facilitation of cardiac alpha 1L-subunit Ca channel current by okadaic acid can be accounted for by a speeding up in the rates of onset during the prepulse. Inhibition of phosphoprotein phosphatases by okadaic acid has only modest effects on the rates of recovery of cardiac alpha 1-subunit Ca channel current from facilitation in the time immediately following the prepulse.

摘要

非洲爪蟾卵母细胞可被选来表达相对高水平的内源性钙电流。这些电流可通过预脉冲得到促进。促进的内源性钙电流不受冈田酸、Rp-cAMPS或二氢吡啶(DHP)拮抗剂(+)PN 200-110的影响。内源性电流以及去极化预脉冲对其的促进作用被1 mM Cd2+完全阻断。相比之下,注射了编码兔心脏α1亚基mRNA的卵母细胞表达的预脉冲促进的钙通道电流,会被磷蛋白磷酸酶抑制剂冈田酸(增强3倍)高度增强,并被Rp-cAMPS和DHP拮抗剂(+)PN 200-110阻断。虽然冈田酸选择性地刺激心脏α1亚基钙电流的预脉冲促进作用,但DHP激动剂(+)SDZ 202-791在很大程度上增加了(5倍)对照电流(预脉冲前)和促进电流(预脉冲后)。(+)SDZ 2只02-791没有阻止Rp-cAMPS或冈田酸对心脏α1亚基促进作用的影响,这表明DHP刺激独立于导致通道促进的磷酸化作用。冈田酸对心脏α1L亚基钙通道电流预脉冲促进作用的增强可归因于预脉冲期间起始速率的加快。冈田酸对磷蛋白磷酸酶的抑制作用对预脉冲后立即从促进状态恢复的心脏α1亚基钙通道电流的恢复速率只有适度影响。

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