title: Angiotensin II decreases spontaneous firing rate of guinea-pig sino-atrial node cells.
abstract: Angiotensin II (Ang II) plays an important role in the regulation of cardiac function, but its electrophysiological effects on sino-atrial (SA) node are not well understood. In this study, the immediate effect of Ang II on action potentials and ionic currents were investigated by using whole-cell patch-clamps in single guinea-pig SA node pacemaker cells. We demonstrated that Ang II exerted a negative effect on spontaneous firing rate, with a concomitant reduction in the slope of diastolic depolarization. The inhibitory effect of Ang II on spontaneous activity displayed a concentration-dependent manner in the range of 1-1000 nM, with IC50 of 8.34 nM. Ang II type 1 (AT1) receptor antagonist valsartan (1 μM) abolished the inhibitory effect. In contrast, Ang II type 2 (AT2) receptor antagonist, PD123319 (1 μM) didn't affect the action of Ang II. Ang II had no significant effect on hyperpolarization-activated current (If) in SA node cells. However, it significantly slowed the deactivation of the slowly activated delayed rectifier K+ current (Iks) and increased the tail current density. Furthermore, Ang II decreased the current density of L-type Ca2+ current in SA node cells. Our data demonstrate that Ang II reduces the auto rhythm of SA node cells via enhancing Iks and reducing ICaL. The result suggests a potential mechanism by which elevated levels of Ang II may be involved in the occurrence of SA node dysfunction in cardiac pathophysiology.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Sheng
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Wang
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004553:Electric Conductivity; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000378:metabolism; D012849:Sinoatrial Node / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D000804:Angiotensin II; D011188:Potassium