| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received January 18, 2002
Accepted after revision April 15, 2002
1 Department of Physiology and Biophysics, University at Buffalo, State University of New York, Buffalo, New York 14214, USA
2 Department of Physiology and Biophysics, University at Buffalo, State University of New York, 124 Sherman Hall, Buffalo, NY 14214, USA
* To whom correspondence should be addressed. E-mail: dc25{at}acsu.buffalo.edu.
The effects of the cholinergic muscarinic agonist carbachol (CCh) on the basal L-type calcium current, ICa,L, in ferret right ventricular (RV) myocytes were studied using whole cell patch clamp. CCh produced two major effects : (i) in all myocytes, extracellular application of CCh inhibited ICa,L in a reversible concentration-dependent manner; and (ii) in many (but not all) myocytes, upon washout CCh produced a significant transient stimulation of ICa,L ('rebound stimulation'). Inhibitory effects could be observed at 1 x 10-10 M CCh. The mean steady-state inhibitory concentration-response relationship was shallow and could be described with a single Hill equation (maximum inhibition = 34.5 %, IC50 = 4 x 10-8 M, Hill coefficient n = 0.60). Steady-state inhibition (1 or 10 µM CCh) had no significant effect on ICa,L selectivity or macroscopic (i) activation characteristics, (ii) inactivation kinetics, (iii) steady-state inactivation or (iv) kinetics of recovery from inactivation. Maximal inhibition of nitric oxide synthase (NOS) activity (preincubation of myocytes in 1 mM L-NMMA (NG-monomethyl-L-arginine) + 1 mM L-NNA (NG-nitro-L-arginine) for 2-3 h plus inclusion of 1 mM L-NMMA + 1 mM L-NNA in the patch pipette solution) produced no significant attenuation of the CCh-mediated inhibition of ICa,L. Protocols involving (i) the nitric oxide (NO) scavenger PTIO (2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide; 200 µM), (ii) imposition of a 'cGMP clamp' (100 µM 8-Bromo-cGMP), and (iii) inhibition of soluble guanylyl cyclase (ODQ (1H-[1,2,4,]oxadiazolo(4,3,-a)quinoxalin-1-one), 50 µM) all failed to attenuate CCh-mediated inhibition of Ica,L. While CCh consistently inhibited basal ICa,L in all RV myocytes studied, not all myocytes displayed rebound stimulation upon CCh washout. However, there was no difference between CCh-mediated inhibition of ICa,L between these two RV myocyte types, and in myocytes displaying rebound stimulation neither ODQ nor 8-Bromo-cGMP (8-Br-cGMP) altered the effect. We conclude that NO production, activation of soluble guanylyl cyclase, or changes in intracellular cGMP levels are not obligatorily involved in muscarinic-mediated modulation of basal ICa,L in ferret RV myocytes.
This article has been cited by other articles:
|
|
 |
|
  J.-B. Shen and A. J. Pappano An Estrogen Metabolite, 2-Methoxyestradiol, Disrupts Cardiac Microtubules and Unmasks Muscarinic Inhibition of Calcium Current J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 507 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Martin, K. Emanuel, C. E. Sears, Y.-H. Zhang, and B. Casadei Are myocardial eNOS and nNOS involved in the {beta}-adrenergic and muscarinic regulation of inotropy? A systematic investigation Cardiovasc Res, April 1, 2006; 70(1): 97 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Y. Lee and C. O. Lee Inhibition of Na+-K+ Pump and L-Type Ca2+ Channel by Glibenclamide in Guinea Pig Ventricular Myocytes J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nygren, A. E. Lomax, and W. R. Giles Heterogeneity of action potential durations in isolated mouse left and right atria recorded using voltage-sensitive dye mapping Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2634 - H2643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. Dedkova, X. Ji, Y. G. Wang, L. A. Blatter, and S. L. Lipsius Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes Circ. Res., December 12, 2003; 93(12): 1233 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Liu, R. H. Kennedy, M. H. Creer, and J. McHowat Alterations in Ca2+ cycling by lysoplasmenylcholine in adult rabbit ventricular myocytes Am J Physiol Cell Physiol, April 1, 2003; 284(4): C826 - C838. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
