![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
K Matsumoto and AJ Pappano
Second Department of Internal Medicine, Saitama University Medical School, Japan.
Carbachol induces a novel tetrodotoxin-resistant Na+ current in guinea pig ventricular myocytes bathed in Tyrode's solution with 20 mM Cs+. This action of carbachol, which initiates a series of reactions that culminates in a catecholamine-independent positive inotropic effect, occurs through muscarinic rather than nicotinic cholinoceptive sites. The concentrations of muscarinic antagonists required to suppress the carbachol-induced current by 50% were 2.1 nM, 270 nM, and 1700 nM for atropine, AF-DX 116, and pirenzepine, respectively. These results indicate that an M2-selective antagonist, AF-DX 116, is more potent than an M1-selective antagonist, pirenzepine, as an inhibitor. The M1- selective agonist McN-A-343 did not induce an inward current and blocked that caused by carbachol, in a rapid and reversible manner. This finding is also consistent with the conclusion that the muscarinic receptor involved in the regulation of myocardial Na+ channels by carbachol cannot be distinguished from the M2 subtype of such receptors. Treatment with pertussis toxin did not affect the ability of carbachol to induce an inward current in ventricular myocytes and reversed the current activated by carbachol in atrial cells from outward to inward. The electrophysiological and pharmacological nature of the carbachol-induced current in ventricular myocytes is very similar to that of the acetylcholine-induced current in Xenopus oocytes transfected with porcine M2, but not M1, muscarinic receptors. In both preparations, Na+ is the dominant charge carrier, intracellular Ca2+ is not involved in opening the Na+ channel, and an M2 receptor is involved.
This article has been cited by other articles:
|
|
 |
|
  P. Gilon and J.-C. Henquin Mechanisms and Physiological Significance of the Cholinergic Control of Pancreatic {beta}-Cell Function Endocr. Rev., October 1, 2001; 22(5): 565 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-W. Dong, C. Tang, and M.-S. Liu Biphasic redistribution of muscarinic receptor and the altered receptor phosphorylation and gene transcription are underlying mechanisms in the rat heart during sepsis Cardiovasc Res, March 1, 2000; 45(4): 925 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-B. Shen, B. Jiang, and A. J. Pappano Lack of Effect of McN-A-343 on Membrane Current and Contraction in Guinea Pig Ventricular Myocytes J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 641 - 648. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Saeki, J.-B. Shen, and A. J. Pappano Inositol-1,4,5-trisphosphate increases contractions but not L-type calcium current in guinea pig ventricular myocytes Cardiovasc Res, March 1, 1999; 41(3): 620 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Protas, J.-B. Shen, and A. J. Pappano Carbachol Increases Contractions and Intracellular Ca++ Transients in Guinea Pig Ventricular Myocytes J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 66 - 74. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Saeki, J.-B. Shen, and A. J. Pappano Carbachol promotes Na+ entry and augments Na/Ca exchange current in guinea pig ventricular myocytes Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1984 - H1993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.G. Wang, J. Huser, L.A. Blatter, and S.L. Lipsius Withdrawal of Acetylcholine Elicits Ca2+-Induced Delayed Afterdepolarizations in Cat Atrial Myocytes Circulation, August 19, 1997; 96(4): 1275 - 1281. [Abstract] [Full Text]
|
|
|
|
 |
|
 V. K. Sharma, H. M. Colecraft, D. X. Wang, A. I. Levey, E. V. Grigorenko, H. H. Yeh, and S.-S. Sheu Molecular and Functional Identification of m1 Muscarinic Acetylcholine Receptors in Rat Ventricular Myocytes Circ. Res., July 1, 1996; 79(1): 86 - 93. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
