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The effects of tertiapin‐Q on responses of the sinoatrial pacemaker of the guinea‐pig heart to vagal nerve stimulation and muscarinic agonists
Author(s) -
Bolter Chris P.,
English Duane J.
Publication year - 2008
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2007.038901
Subject(s) - acetylcholine , medicine , muscarinic acetylcholine receptor , stimulation , vagus nerve , endocrinology , bradycardia , chemistry , vagus nerve stimulation , heart rate , receptor , blood pressure
Using Langendorff preparations of the guinea‐pig heart, we have examined the participation of the acetylcholine (ACh)‐activated potassium channel, I K,ACh , in the bradycardia produced by electrical stimulation of the vagus (parasympathetic) nerve and muscarinic agonists (ACh and bethanecol, bolus i.a .). Hearts from young animals (160–250 g) were perfused with Krebs–Henseleit solution, and pacemaker frequency was determined from the P wave of an ECG. Tertiapin‐Q was used to block I K,ACh . Vagal stimulation (10 s trains at 2, 5 and 10 Hz) produced graded reductions in atrial rate that were substantially attenuated, and to a similar extent, by 300 n m and 1 μ m tertiapin‐Q (to 0.42 ± 0.12, mean ± s.d., of the control values; P < 0.001). Acetylcholine (3 nmol) produced brief graded bradycardias that were also attenuated by tertiapin‐Q (0.24 ± 0.24; P = 0.006). Similar results were obtained when experiments were repeated in 2 m m Cs + (to block the hyperpolarization‐activated pacemaker current). Bethanecol (30, 50 and 70 nmol), a muscarinic agonist with no appreciable nicotinic activity, produced sustained bradycardias that were attenuated by 300 n m tertiapin‐Q (0.36 ± 0.21; P < 0.0001). The responses to vagal stimulation and ACh developed more slowly in tertiapin‐Q, indicating that a rapidly acting mechanism had been blocked. Responses to vagal stimulation were faster in 2 m m Cs + . Together, these observations show that ACh released from parasympathetic nerve varicosities exerts a considerable part of its effect on the pacemaker by activating I K,ACh and acts in a manner not readily distinguishable from that of directly applied muscarinic agonists.