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Am J Physiol Heart Circ Physiol 273: H2155-H2160, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 5, H2155-H2160, November 1997

Effects of ionic channel antagonists barium, cesium, and UL-FS-49 on vagal slowing of atrial rate in dogs

Don W. Wallick, Akin Kuguoglu, Tianen Yang, Sherry L. Stuesse, and Matthew N. Levy

Division of Investigative Medicine, Mt. Sinai Medical Center, Cleveland 44106; and Department of Neurobiology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272

In response to a brief vagal stimulus, the atrial rate initially slows, then transiently accelerates, and slows a second time. We determined the effects of three antagonists to two ionic channels on this characteristic triphasic pacemaker response. Brief bursts of vagal stimulation were delivered to anesthetized dogs, and atrial cycle lengths were recorded. Either barium, cesium, or UL-FS-49 was administered. Barium, which primarily blocks the acetylcholine-sensitive potassium current (IK,ACh), attenuated the initial vagally induced bradycardia by >50% without affecting the subsequent acceleration or the secondary slowing. Cesium and UL-FS-49 [both of which primarily block the pacemaker current (If)] did not affect the initial vagal slowing of atrial rate but abolished the acceleratory portion of the response. The secondary slowing was abolished by cesium but not by UL-FS-49. We conclude that the initial rapid atrial response to acetylcholine is mediated mainly by the IK,ACh, with little contribution from the If. The subsequent acceleration is mediated by activation of the If.

acetylcholine; autonomic nervous system; heart rate; vagus nerves; parasympathetic; ionic currents; cardiac pacemaker


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