JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yamada, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamada, M.

Vol. 300, Issue 2, 681-687, February 2002

The Role of Muscarinic K+ Channels in the Negative Chronotropic Effect of a Muscarinic Agonist

Mitsuhiko Yamada

Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Osaka, Japan

Acetylcholine causes bradycardia through M2 muscarinic receptors in sinoatrial node cells. I examined with electrocardiogram how the muscarinic K+ (KACh) channel participates in the sinus bradycardia induced by a muscarinic agonist in the Langendorff preparation of rabbit hearts. In the presence of 100 nM propranolol, 1 nM to 10 µM carbachol (CCh) induced sinus bradycardia in a concentration-dependent manner. Tertiapin (100 or 300 nM), which selectively blocks KACh channels in cardiac myocytes, significantly inhibited the effect of >= 300 nM but not <= 100 nM CCh. The effect of CCh was divided into tertiapin-sensitive and -insensitive components. The former component was induced by >100 nM CCh in a concentration-dependent manner and accounted for ~75% of the maximum effect of CCh. The KACh channel in atrial myocytes was also activated by this range of concentrations of CCh as measured with the patch-clamp method. The tertiapin-insensitive component was induced by 1 to 300 nM CCh in a concentration-dependent manner and accounted for ~25% of the maximum effect of CCh. The sinus rate in the presence of 1 µM CCh and 300 nM tertiapin was similar to that in the presence of 2 mM CsCl, a blocker of the hyperpolarization-activated If current. Furthermore, no tertiapin-insensitive component existed in the presence of 2 mM CsCl. Therefore, the negative chronotropic effect of >= 300 nM CCh is mainly mediated by KACh channels, whereas that of <= 100 nM CCh may result from suppression of the If current.

0022-3565/02/3002-0681$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
M. E. Mangoni and J. Nargeot
Genesis and Regulation of the Heart Automaticity
Physiol Rev, July 1, 2008; 88(3): 919 - 982.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
K. Bender, P. Nasrollahzadeh, M. Timpert, B. Liu, L. Pott, and M.-C. Kienitz
A role for RGS10 in {beta}-adrenergic modulation of G-protein-activated K+ (GIRK) channel current in rat atrial myocytes
J. Physiol., April 15, 2008; 586(8): 2049 - 2060.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. K. Landeen, D. A. Dederko, C. S. Kondo, B. S. Hu, N. Aroonsakool, J. H. Haga, and W. R. Giles
Mechanisms of the negative inotropic effects of sphingosine-1-phosphate on adult mouse ventricular myocytes
Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H736 - H749.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. P. Ye, S. Z. Duan, D. S. Milstone, and R. M. Mortensen
Go controls the hyperpolarization-activated current in embryonic stem cell-derived cardiocytes
Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H979 - H985.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
C. P. Bolter and D. J. English
The effects of tertiapin-Q on responses of the sinoatrial pacemaker of the guinea-pig heart to vagal nerve stimulation and muscarinic agonists
Exp Physiol, January 1, 2008; 93(1): 53 - 63.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Mizuno, A. Kamiya, T. Kawada, T. Miyamoto, S. Shimizu, and M. Sugimachi
Muscarinic potassium channels augment dynamic and static heart rate responses to vagal stimulation
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1564 - H1570.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. L. Marker, R. Lujan, H. H. Loh, and K. Wickman
Spinal G-Protein-Gated Potassium Channels Contribute in a Dose-Dependent Manner to the Analgesic Effect of {micro}- and {delta}- But Not {kappa}-Opioids
J. Neurosci., April 6, 2005; 25(14): 3551 - 3559.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
E. N. Nikolov and T. T. Ivanova-Nikolova
Functional Characterization of a Small Conductance GIRK Channel in Rat Atrial Cells
Biophys. J., November 1, 2004; 87(5): 3122 - 3136.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
J. R. Ehrlich, T.-J. Cha, L. Zhang, D. Chartier, L. Villeneuve, T. E. Hebert, and S. Nattel
Characterization of a hyperpolarization-activated time-dependent potassium current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium
J. Physiol., June 1, 2004; 557(2): 583 - 597.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. B. Scheidweiler, M. A. Plessinger, J. Shojaie, R. W. Wood, and T. C. Kwong
Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate
J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1179 - 1187.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.