Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
J Cardiovasc Electrophysiol. 2011 Jan;22(1):71-80. doi: 10.1111/j.1540-8167.2010.01839.x.
Oscillatory Mechanisms in Sinus Node Cholinergic Control.
The role of the oscillatory after-potential V(os) and pre-potential ThV(os) in cholinergic control of discharge was studied in sino-atrial node (SAN).
A microelectrode technique was used in isolated guinea-pig SAN superfused in vitro in high K(+) to visualize V(os) and ThV(os) . The cholinergic agonist carbachol (CCh) decreased the amplitude and slope of V(os) and ThV(os) at a time when there was no increase in maximum diastolic potential. The slowing in SAN rate was due to slower and smaller ThV(os) that missed intermittently the threshold and occurred gradually later in diastole, but not to a decrease in the intrinsic rate of ThV(os) . Eventually, quiescence followed. Larger CCh concentrations quickly induced a hyperpolarization that altogether prevented the occurrence of oscillatory potentials. During CCh washout, ThV(os) reappeared and consistently reinitiated discharge. Lower Ca(2+) also decreased slopes and amplitude of V(os) and ThV(os) , thereby slowing and stopping SAN discharge, as CCh did. Overdrive temporarily offset the negative chronotropic effects of CCh and of low Ca(2+) Cesium (a blocker of hyperpolarization-activated current I(f) ) did not abolish CCh inhibitory effects on oscillatory potentials.
The cholinergic agonist CCh: (1) slows SAN discharge by decreasing the amplitude of V(os) and ThV(os) , but not the rate of ThV(os) ; (2) can cause hyperpolarization that altogether suppresses the oscillatory potentials; (3) is mimicked in its effects by low Ca(2+) ; (4) is antagonized by procedures that increase cellular calcium; and (5) modifies the oscillatory potentials independently of I(f) .
窦房结胆碱能控制中的振荡机制。
本研究探讨了振荡后电位 V(os) 和前电位 ThV(os) 在窦房结 (SAN) 胆碱能控制放电中的作用。
使用微电极技术，在体外高 [K(+)] (o) 灌流的分离豚鼠 SAN 中，可视化 V(os) 和 ThV(os) 。胆碱能激动剂卡巴胆碱 (CCh) 降低了 V(os) 和 ThV(os) 的幅度和斜率，而最大舒张电位没有增加。SAN 率的减慢是由于 ThV(os) 变慢且变小，间歇性错过阈电位，并且在舒张期发生得更晚，但不是由于 ThV(os) 的固有率降低。最终，出现静止。较大的 CCh 浓度迅速诱导超极化，完全阻止了振荡电位的发生。在 CCh 洗脱期间，ThV(os) 重新出现并一致重新引发放电。较低的 [Ca(2+)] (o) 也降低了 V(os) 和 ThV(os) 的斜率和幅度，从而像 CCh 一样减慢并停止 SAN 放电。超速驱动暂时抵消了 CCh 和低 [Ca(2+)] (o) 的负变时作用。铯 (一种超极化激活电流 I(f) 的阻断剂) 并没有消除 CCh 对振荡电位的抑制作用。
胆碱能激动剂 CCh：(1) 通过降低 V(os) 和 ThV(os) 的幅度而不是 ThV(os) 的速率来减慢 SAN 放电；(2) 可以引起超极化，完全抑制振荡电位；(3) 在作用上被低 [Ca(2+)] (o) 模拟；(4) 被增加细胞内钙的程序拮抗；(5) 独立于 I(f) 改变振荡电位。
