title: Muscarinic potassium channels augment dynamic and static heart rate responses to vagal stimulation.
abstract: 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.
authors.affiliation: Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. m-mizuno@ri.ncvc.go.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizuno
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kamiya
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Shimizu
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D001514:Bee Venoms; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic; C029738:tertiapin; D000109:Acetylcholine