Rubenstein D S, Lipsius S L
Department of Physiology, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 60153.
Circ Res. 1989 Apr;64(4):648-57. doi: 10.1161/01.res.64.4.648.
Intracellular recordings were made from eustachian ridge of cat right atrium to determine mechanisms responsible for subsidiary pacemaker automaticity. Pacemaker action potentials exhibited two phases of diastolic depolarization: an initial steeper slope (D1) followed by a more gradual slope (D2). Cesium (1 mM) decreased D1 (-45.6%) to a significantly greater extent than D2 (-33.6%) and increased spontaneous cycle length (SCL) (+37.7%). Tetrodotoxin (10(-6) M) had no effect on maximum rate of rise of upstroke, although it increased SLC (+23.9%). Verapamil (0.4-1.0 microM) progressively increased SCL by decreasing late diastolic slope, resulting in oscillatory potentials and eventual quiescence. Both norepinephrine (2 x 10(-9) M) and Bay K 8644 (10(-7) M) elicited a significantly greater increase in D2 than in D1, resulting in a decrease in SCL. Ryanodine (10(-6) M) caused a small but significant initial decrease (-3.7%) followed by a progressive increase in SCL (+172%). Ryanodine decreased D2 without changing D1, increased maximum rate of rise and overshoot potential, and abolished tension. In the presence of ryanodine, Bay K 8644 progressively increased D1 amplitude, resulting in a cyclic pattern of dysrhythmic activity. In the presence of ryanodine, cesium significantly decreased D1 (-39.3%), shifted the late diastolic potential more negative, and increased SCL (+25.7%). These results indicated that multiple mechanisms participate in subsidiary pacemaker automaticity. They include 1) a cesium-sensitive component that contributes to a greater extent during the initial phase of diastolic depolarization, 2) a component mediated via calcium released from the sarcoplasmic reticulum that contributes primarily during the latter half of diastolic depolarization, and 3) possibly a direct contribution by the slow inward calcium current.
通过对猫右心房咽鼓管嵴进行细胞内记录，以确定负责次级起搏点自律性的机制。起搏动作电位表现出舒张期去极化的两个阶段：初始较陡的斜率（D1），随后是较平缓的斜率（D2）。铯（1 mM）使D1降低的幅度（-45.6%）显著大于D2（-33.6%），并增加了自发周期长度（SCL）（+37.7%）。河豚毒素（10⁻⁶ M）对动作电位上升支的最大上升速率没有影响，尽管它增加了SLC（+23.9%）。维拉帕米（0.4 - 1.0 μM）通过降低舒张期末期斜率逐渐增加SCL，导致振荡电位并最终静止。去甲肾上腺素（2×10⁻⁹ M）和Bay K 8644（10⁻⁷ M）引起的D2增加幅度均显著大于D1，导致SCL降低。ryanodine（10⁻⁶ M）最初引起小幅但显著的降低（-3.7%），随后SCL逐渐增加（+172%）。ryanodine降低D2但不改变D1，增加动作电位上升支的最大上升速率和超射电位，并消除张力。在存在ryanodine的情况下，Bay K 8644逐渐增加D1幅度，导致出现节律异常活动的循环模式。在存在ryanodine的情况下，铯显著降低D1（-39.3%），使舒张期末期电位更负，并增加SCL（+25.7%）。这些结果表明多种机制参与次级起搏点自律性。它们包括：1）一种对铯敏感的成分，在舒张期去极化的初始阶段贡献更大；2）一种通过肌浆网释放的钙介导的成分，主要在舒张期去极化的后半期起作用；3）可能是缓慢内向钙电流的直接贡献。
