Muscarinic inhibition of basal L-type calcium current in pacemaker cells from the rabbit atrioventricular node

Effects of acetylcholine (ACh) on the L-type calcium current were examined in isolated atrioventricular nodal cells that exhibited spontaneous contractions. ACh (0.1 to 10 microM) inhibited basal calcium current dose-dependently. This inhibition was eliminated by dialysis with 8Br cAMP or cAMP-dependent kinase inhibitory peptide. Both extracellular N-ethylmaleimide 50 microM and intracellular GDPssS 0.2 mM abolished the ACh effect. Dialysis with cGMP or NG-monomethyl-L-arginine did not significantly affect ACh inhibition of basal calcium current. Similarly, cGMP-dependent protein kinase inhibitor KT5823 (1 microM) and the type II phosphodiesterase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (30 microM) did not attenuate the ACh effect. Therefore, ACh inhibits the basal calcium current in the atrioventricular node mainly by suppressing cAMP synthesis through the inhibitory GTP-binding protein.