Muscarinic potassium channels augment dynamic and static heart rate responses to vagal stimulation

Vagal control of heart rate (HR) is mediated by direct and indirect actions of ACh. Direct action of ACh activates the muscarinic K⁺ (K _ACh) channels, whereas indirect action inhibits adenylyl cyclase. The role of the K_ACh channels in the overall picture of vagal HR control remains to be elucidated. We examined the role of the K_ACh channels in the transfer characteristics of the HR response to vagal stimulation. In nine anesthetized sino-aortic-denerved and vagotomized rabbits, the vagal nerve was stimulated with a binary white-noise signal (0-10 Hz) for examination of the dynamic characteristic and in a step-wise manner (5, 10, 15, and 20 Hz/min) for examination of the static characteristic. The dynamic transfer function from vagal stimulation to HR approximated a first-order, low-pass filter with a lag time. Tertiapin, a selective K_ACh channel blocker (30 nmol/kg iv), significantly decreased the dynamic gain from 5.0 ± 1.2 to 2.0 ± 0.6 (mean ± SD) beats·min^-1·Hz^-1 (P < 0.01) and the corner frequency from 0.25 ± 0.03 to 0.06 ± 0.01 Hz (P < 0.01) without changing the lag time (0.37 ± 0.04 vs. 0.39 ± 0.05 s). Moreover, tertiapin significantly attenuated the vagal stimulation-induced HR decrease by 46 ± 21, 58 ± 18, 65 ± 15, and 68 ± 11% at stimulus frequencies of 5, 10, 15, and 20 Hz, respectively. We conclude that K_ACh channels contribute to a rapid HR change and to a larger decrease in the steady-state HR in response to more potent tonic vagal stimulation.