Regional difference in dynamical property of sinoatrial node pacemaking: Role of Na+ channel current
Regional difference in dynamical property of sinoatrial node pacemaking: Role of Na+ channel current
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DOI：
10.1529/biophysj.107.112854
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发表时间：
2008-07-15
影响因子：
3.4
通讯作者：
Shibamoto, Toshishige
中科院分区：
文献类型：
--
作者：
Kurata, Yasutaka;Matsuda, Hiroyuki;Shibamoto, Toshishige
为了阐明窦房结起搏机制的区域差异，我们研究了1）、中央和外周细胞电流阻滞或超极化期间的分叉结构，2），分叉结构区域差异的离子基础，以及3），Na+通道电流（I-Na）在外周细胞起搏中的作用。对兔窦房结中央和周围细胞的数学模型进行分叉分析；平衡点、周期轨道及其稳定性被确定为参数的函数。还评估了针对应用乙酰胆碱或心房电紧张调节的结构稳定性。阻断 L 型 Ca2+ 通道电流 (I-Ca, L) 可稳定平衡点并消除中心和外周的起搏。停止起搏器的临界乙酰胆碱浓度和间隙连接电导在外周高于中心，通过阻断 I-Na 显着降低。在超极化条件下，阻断 I-Na，但不消除 I-Ca、L，会消除外周细胞起搏。这些结果表明：1)、I-Ca、L 负责中枢和外周细胞的基础起搏；2)、外周细胞比中枢细胞更能承受超极化负荷；3)、I-Na 提高了超极化负荷的结构稳定性；4)、I-Na 依赖性起搏在超极化外周细胞中是可能的。
To elucidate the regional differences in sinoatrial node pacemaking mechanisms, we investigated 1), bifurcation structures during current blocks or hyperpolarization of the central and peripheral cells, 2), ionic bases of regional differences in bifurcation structures, and 3), the role of Na+ channel current (I-Na) in peripheral cell pacemaking. Bifurcation analyses were performed for mathematical models of the rabbit sinoatrial node central and peripheral cells; equilibrium points, periodic orbits, and their stability were determined as functions of parameters. Structural stability against applications of acetylcholine or electrotonic modulations of the atrium was also evaluated. Blocking L-type Ca2+ channel current (I-Ca, L) stabilized equilibrium points and abolished pacemaking in both the center and periphery. Critical acetylcholine concentration and gap junction conductance for pacemaker cessation were higher in the periphery than in the center, being dramatically reduced by blocking I-Na. Under hyperpolarized conditions, blocking I-Na, but not eliminating I-Ca, L, abolished peripheral cell pacemaking. These results suggest that 1), I-Ca, L is responsible for basal pacemaking in both the central and peripheral cells, 2), the peripheral cell is more robust in withstanding hyperpolarizing loads than the central cell, 3), I-Na improves the structural stability to hyperpolarizing loads, and 4), I-Na-dependent pacemaking is possible in hyperpolarized peripheral cells.