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This Article Full Text Full Text (PDF) All Versions of this Article: 542/1/107    most recent 2002.017335v2 2002.017335v1 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Bett, G. C. L. Articles by Campbell, D. L. Search for Related Content PubMed PubMed Citation Articles by Bett, G. C. L. Articles by Campbell, D. L.

Cholinergic modulation of the basal L-type calcium current in ferret right ventricular myocytes

Glenna C. L. Bett, Shuiping Dai and Donald L. Campbell

The effects of the cholinergic muscarinic agonist carbachol (CCh) on the basal L-type calcium current, I_Ca,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 I_Ca,L in a reversible concentration-dependent manner; and (ii) in many (but not all) myocytes, upon washout CCh produced a significant transient stimulation of I_Ca,L ('rebound stimulation'). Inhibitory effects could be observed at 1 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 10^-8 M, Hill coefficient n = 0.60). Steady-state inhibition (1 or 10 µM CCh) had no significant effect on I_Ca,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 (N^G-monomethyl-L-arginine) + 1 mM L-NNA (N^G-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 I_Ca,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 I_ca,L. While CCh consistently inhibited basal I_Ca,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 I_Ca,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 I_Ca,L in ferret RV myocytes.

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