Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels

Abstract

Although muscarinic K+ (KACh) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the KACh channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K ACh channel blocker, decreased the dynamic gain (to 2.3 ± 0.9 beats·min-1·Hz-1, from 4.6 ± 1.1, P < 0.01, mean ± SD) and the corner frequency (to 0.05 ± 0.01 Hz, from 0.26 ± 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6 ± 1.0 beats·min-1·Hz-1, from 7.3 ± 1.1, P < 0.01) and the corner frequency (to 0.06 ± 0.02 Hz, from 0.23 ± 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the KACh channels. The rapidity of the HR response obtained by the KACh channel pathway was robust during the accentuated antagonism.