PMID: 8596736Mar 1, 1996Paper

Activation of the hyperpolarization-activated current (if) in sino-atrial node myocytes of the rabbit by vasoactive intestinal peptide

Pflügers Archiv : European journal of physiology
E A AcciliD DiFrancesco

Abstract

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter found in extrinsic and intrinsic nerves of the heart. VIP can be released by vagal stimulation but, contrary to ACh, causes positive chronotropic effects as a result of binding to cardiac receptors which stimulate adenylate cyclase, and thus has been implicated in vagal tachycardias. Since the rate of diastolic depolarization of sinoatrial (SA) node myocytes depends on the hyperpolarization-activated current (if), which is directly activated by cytoplasmic cAMP, we studied the action of VIP on if in myocytes isolated from the SA node of the rabbit. VIP (0.65 microM) reversibly increased if at -65 mV but had no effect at -115 mV suggesting that its primary effect was to shift the activation curve to more positive voltages. Hyperpolarizing ramp and voltage compensation protocols indicated that VIP shifts the activation curve of if by approximately 5-6 mV in the positive direction with no change in maximal conductance. This shift may be the mechanism by which VIP produces its positive chronotropic effect and supports a negative feedback role for this peptide during elevated vagal activity.

Citations

Dec 19, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Peng-Sheng ChenShien-Fong Lin
Feb 3, 2009·International Journal of Cardiology·Arie O VerkerkRonald Wilders
Jul 16, 2008·Physiological Reviews·Matteo E Mangoni, Joël Nargeot
Oct 19, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Analyne SchroederChristopher S Colwell
Dec 25, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Chian P YeRichard M Mortensen

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