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This Article Full Text Full Text (PDF) All Versions of this Article: 93/1/53    most recent expphysiol.2007.038901v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bolter, C. P. Articles by English, D. J. Search for Related Content PubMed PubMed Citation Articles by Bolter, C. P. Articles by English, D. J.

¹ University of Otago, Dunedin, New Zealand

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 nM and 1 µM 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 mM 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 nM 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 mM 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.

(Received 13 June 2007; accepted after revision 20 August 2007; first published online 24 August 2007)
Corresponding author C. P. Bolter: Department of Physiology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin 9054, New Zealand. Email: chris.bolter{at}stonebow.otago.ac.nz