Membrane potential fluctuations resulting from submembrane Ca2+ releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state
Membrane potential fluctuations resulting from submembrane Ca2+ releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state
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DOI：
10.1161/01.res.0000247933.66532.0b
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发表时间：
2006-10-27
影响因子：
20.1
通讯作者：
Lakatta, Edward G.
中科院分区：
文献类型：
--
作者：
Bogdanov, Konstantin Y.;Maltsev, Victor A.;Lakatta, Edward G.
在兔窦房结起搏细胞舒张期去极化晚期，随机但大致周期性的LCR((L)在局部肌膜下兰尼定受体介导的(C)在BARA(2+)释放下)通过Na+/Ca~(2+)交换产生内向电流(I-Ncx)。虽然LCR特征与自发搏动相关，但LCR特征与SANC自发搏动频率之间的具体联系，即LCR对DD精细结构的影响，还没有明确的定义。在这里，我们确定了LCRs和生成的INCX如何影响DD精细结构，以控制自发SARC激发速率。膜电位(V-m)记录与共聚焦钙测量相结合显示，LCR向DD后部传递一个非线性的指数上升相位，表现出幅度约为2 mV的搏动Vm波动。改变非线性DD的LCR时间或幅度的动作(ryanodine、BAPTA、硝苯地平或异丙肾上腺素)在非线性DD成分的Vm波动中产生相应的变化，这些动作引起的V-m波动反应与这些扰动引起的自发搏动频率的同步变化密切相关。利用在这些扰动下测量的LCR特性，数值模拟预测了一族局部I-NCX，它再现了实验测量的Vm波动，并确定了非线性DD分量的起始和幅度以及搏动频率。因此，DD后期的节拍Vm波动反映了潜在的LCR/I-NCX事件，这些事件的集合形成了最终控制SANC变时性状态的非线性DD分量，并与表膜离子通道紧密合作。
Stochastic but roughly periodic LCRs ((L) under bar ocal subsarcolemmal ryanodine receptor-mediated (C) under bara(2+) Releases) during the late phase of diastolic depolarization ( DD) in rabbit sinoatrial nodal pacemaker cells (SANCs) generate an inward current (I-NCX) via the Na+/Ca2+ exchanger. Although LCR characteristics have been correlated with spontaneous beating, the specific link between LCR characteristics and SANC spontaneous beating rate, ie, impact of LCRs on the fine structure of the DD, have not been explicitly defined. Here we determined how LCRs and resultant INCX impact on the DD fine structure to control the spontaneous SANC firing rate. Membrane potential (V-m) recordings combined with confocal Ca2+ measurements showed that LCRs impart a nonlinear, exponentially rising phase to the DD later part, which exhibited beat-to-beat Vm fluctuations with an amplitude of approximately 2 mV. Maneuvers that altered LCR timing or amplitude of the nonlinear DD (ryanodine, BAPTA, nifedipine or isoproterenol) produced corresponding changes in Vm fluctuations during the nonlinear DD component, and the V-m fluctuation response evoked by these maneuvers was tightly correlated with the concurrent changes in spontaneous beating rate induced by these perturbations. Numerical modeling, using measured LCR characteristics under these perturbations, predicted a family of local I-NCX that reproduced Vm fluctuations measured experimentally and determined the onset and amplitude of the nonlinear DD component and the beating rate. Thus, beat-to-beat Vm fluctuations during late DD phase reflect the underlying LCR/I-NCX events, and the ensemble of these events forms the nonlinear DD component that ultimately controls the SANC chronotropic state in tight cooperation with surface membrane ion channels.