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

¹Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, and ³Morinomiya University of Medical Sciences, Osaka; and ²Japan Association for the Advancement of Medical Equipment, Tokyo, Japan

Submitted 23 March 2007 ; accepted in final form 22 May 2007

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 sinoaortic-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.

systems analysis; transfer function; muscarinic receptor; rabbit

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				T. Kawada, M. Mizuno, S. Shimizu, K. Uemura, A. Kamiya, and M. Sugimachi Angiotensin II disproportionally attenuates dynamic vagal and sympathetic heart rate controls Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1666 - H1674. [Abstract] [Full Text] [PDF]