Regulation of cardiac pacemaker current If in excised membranes from sinoatrial node cells.
Regulation of cardiac pacemaker current If in excised membranes from sinoatrial node cells.
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窦房结细胞切除膜中心脏起搏器电流 If 的调节。
DOI：
10.1152/ajpheart.1990.258.6.h1947
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Brown,AM
中科院分区：
文献类型：
--
作者：
Yatani,A;Brown,AM
我们提出，电压门控离子通道受受体-鸟嘌呤-核苷酸结合（G）蛋白途径的调节，这些途径是膜界定（直接）或细胞质（间接）的。由于已知间接途径将毒蕈碱和β-肾上腺素受体与超极化激活电流（If）通道耦合，因此我们通过使用千兆密封膜片钳方法测量兔窦房结细胞中的If电流来检验我们的假设，即直接途径也可能存在。 β-激动剂异丙肾上腺素 (Iso) 增加全细胞 If 电流，而毒蕈碱激动剂卡巴胆碱 (Carb) 则降低全细胞 If 电流，其速率与卡巴胆碱增加相同细胞中毒蕈碱 K(+)-乙酰胆碱通道 (K+[ACh]) 电流的速率相似。 K+[ACh] 电流直接由 G 蛋白门控，因此结果支持我们的假设。在我们首次确定可以在没有细胞质底物的情况下从内向外切下的膜片中记录 If 后，得到了更强有力的支持。在这些条件下，如果提供鸟苷5'-三磷酸和Mg 2+ 存在，则Iso增加且Carb减少，无细胞斑块存在。因此，G 蛋白可能通过直接作用将自主受体与质膜内的 If 偶联。
We have proposed that voltage-gated ionic channels are regulated by receptor-guanine-nucleotide binding (G) protein pathways that are membrane delimited (direct) or cytoplasmic (indirect). Since indirect pathways are known to couple muscarinic and beta-adrenergic receptors to hyperpolarization-activated current (If) channels, we tested our hypothesis that direct pathways might also be present by measuring If currents in rabbit sinoatrial node cells using the gigaseal patch clamp method. Whole cell If currents were increased by the beta-agonist isoproterenol (Iso) and decreased by the muscarinic agonist carbachol (Carb) at rates that were similar to the rate at which carbachol increased muscarinic K(+)-acetylcholine channel (K+[ACh]) current in the same cells. K+[ACh] currents are directly gated by a G protein, and the results therefore supported our hypothesis. Much stronger support came after we established for the first time that If could be recorded from excised inside out membrane patches in the absence of cytoplasmic substrates. Under these conditions Iso increased and Carb decreased cell-free patch If provided guanosine 5'-triphosphate and Mg2+ were present. Thus G proteins couple autonomic receptors to If within the plasma membrane, probably by a direct action.