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心脏浦肯野纤维起搏电流I(Kdd)的变迁

The vicissitudes of the pacemaker current I (Kdd) of cardiac purkinje fibers.

作者信息

Vassalle Mario

机构信息

Department of Physiology and Pharmacology, Box 31 State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.

出版信息

J Biomed Sci. 2007 Nov;14(6):699-716. doi: 10.1007/s11373-007-9182-2. Epub 2007 Jun 12.

Abstract

The mechanisms underlying the pacemaker current in cardiac tissues is not agreed upon. The pacemaker potential in Purkinje fibers has been attributed to the decay of the potassium current I (Kdd). An alternative proposal is that the hyperpolarization-activated current I (f) underlies the pacemaker potential in all cardiac pacemakers. The aim of this review is to retrace the experimental development related to the pacemaker mechanism in Purkinje fibers with reference to findings about the pacemaker mechanism in the SAN as warranted. Experimental data and their interpretation are critically reviewed. Major findings were attributed to K(+) depletion in narrow extracellular spaces which would result in a time dependent decay of the inward rectifier current I (K1). In turn, this decay would be responsible for a "fake" reversal of the pacemaker current. In order to avoid such a postulated depletion, Ba(2+) was used to block the decay of I (K1). In the presence of Ba(2+) the time-dependent current no longer reversed and instead increased with time and more so at potentials as negative as -120 mV. In this regard, the distinct possibility needs to be considered that Ba(2+) had blocked I (Kdd) (and not only I (K1)). That indeed this was the case was demonstrated by studying single Purkinje cells in the absence and in the presence of Ba(2+). In the absence of Ba(2+), I (Kdd) was present in the pacemaker potential range and reversed at E (K). In the presence of Ba(2+), I (Kdd) was blocked and I (f) appeared at potentials negative to the pacemaker range. The pacemaker potential behaves in a manner consistent with the underlying I (Kdd) but not with I (f). The fact that I (f) is activated on hyperpolarization at potential negative to the pacemaker range makes it suitable as a safety factor to prevent the inhibitory action of more negative potentials on pacemaker discharge. It is concluded that the large body of evidence reviewed proves the pacemaker role of I (Kdd) (but not of I (f)) in Purkinje fibers.

摘要

心脏组织中起搏电流的潜在机制尚无定论。浦肯野纤维中的起搏电位曾被认为归因于钾电流I(Kdd)的衰减。另一种观点认为,超极化激活电流I(f)是所有心脏起搏器中起搏电位的基础。本综述的目的是根据窦房结起搏机制的相关研究结果,必要时追溯与浦肯野纤维起搏机制相关的实验进展。对实验数据及其解释进行了严格审查。主要发现归因于狭窄细胞外空间中的钾离子耗竭,这会导致内向整流电流I(K1)随时间衰减。反过来,这种衰减将导致起搏电流的“假”反转。为了避免这种假定的耗竭,使用钡离子(Ba(2+))来阻断I(K1)的衰减。在存在Ba(2+)的情况下,随时间变化的电流不再反转,而是随时间增加,在负至-120 mV的电位下增加得更多。在这方面,需要考虑一种明显的可能性,即Ba(2+)阻断了I(Kdd)(而不仅仅是I(K1))。通过研究有无Ba(2+)存在时的单个浦肯野细胞,证实了情况确实如此。在没有Ba(2+)的情况下,I(Kdd)存在于起搏电位范围内,并在钾离子平衡电位(E(K))处反转。在存在Ba(2+)的情况下,I(Kdd)被阻断,I(f)出现在低于起搏电位范围的负电位处。起搏电位的行为与潜在的I(Kdd)一致,而与I(f)不一致。I(f)在低于起搏电位范围的负电位超极化时被激活,这一事实使其适合作为一种安全因素,以防止更负电位对起搏放电的抑制作用。结论是,所审查的大量证据证明了I(Kdd)(而非I(f))在浦肯野纤维中的起搏作用。

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