Studies on the bradycardia and periodic rhythm caused by veratramine in the sinoatrial node of the guinea pig.

Abstract

In spontaneously beating, isolated guinea pig sinus-atria, veratramine (2.44 microM) slowed the rate of spontaneous depolarization of sinoatrial node cells throughout diastole, markedly slowed the frequency, and often (especially in the presence of high extracellular Ca2+) induced a periodic rhythm. This rhythm consisted of periods of complete inactivity (inactive phases) alternating with periods of apparently normal beating (active phases), with a rising and falling (parabolic) frequency pattern like that of neuronal burst firing. Slight mechanical deformation of the sinoatrial node markedly attenuated the effects of veratramine, and periodic rhythm could not be produced when the sinoatrial node was pinned down for immobilization. During the active phase of periodic rhythm, the rate of spontaneous diastolic depolarization (pacemaker potential) in pacemaker cells rose and fell with the frequency, while contrariwise, the maximum rate of depolarization fell and then rose. The last beat in the active phase was followed by a small transient afterdepolarization, which had the appearance of an abortive pacemaker potential that failed to reach threshold for triggering an action potential. The effects of various programs of electrical stimulation and pacing indicated that activity of the sinoatrial node, whether spontaneous or driven, has two effects on the amplitude of afterdepolarization, a short-lasting cumulative facilitory effect and a long-lasting cumulative inhibitory effect. Veratramine periodic rhythm arises from the interplay of these two effects, with abrupt cessation of beating whenever the afterdepolarization amplitude falls below the threshold for triggering an action potential. It is suggested that the inhibitory effect may be due to inactivation of the slow inward current and the facilitory effect may be due to one or more of the depolarizing currents activated by intracellular Ca2+.

• Authors: C D Thron, F V McCann
• Journal: Journal of electrocardiology (J Electrocardiol) Vol. 31 Issue 3 Pg. 257-68 (Jul 1998) ISSN: 0022-0736 [Print] United States
• PMID: 9682902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Muscarinic Antagonists
• Veratrum Alkaloids
• Atropine
• Propranolol
• veratramine

Topics

• Action Potentials (drug effects)
• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Atropine (pharmacology)
• Bradycardia (chemically induced, physiopathology)
• Cardiac Pacing, Artificial
• Electrophysiology
• Guinea Pigs
• Heart Rate (drug effects)
• In Vitro Techniques
• Membrane Potentials (drug effects)
• Muscarinic Antagonists (pharmacology)
• Propranolol (pharmacology)
• Sinoatrial Node (drug effects, physiopathology)
• Veratrum Alkaloids (pharmacology)