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 exam ined in isolated atrioventricular nodal cells that exhib ited spontane ous contractions. ACh (0.1 to 10 mu M) 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 mu M and intracellular GDP beta S 0.2 mM abolished the ACh effect. Dialysis with cGMP or NG-monomethyl-L-arginine did no t significantly affect ACh inhibition of basal calcium current. Simila rly, cGMP dependent protein kinase inhibitor KT5823 (1 mu M) and the t ype II phosophodiesterase inhibitor erythro-9-(2-hydroxy-3-nonyl) aden ine (30 mu M) did not attenuate the ACh effect. Therefore, ACh inhibit s the basal calcium current in the atrioventricular node mainly by sup pressing cAMP synthesis through the inhibitory GTP-binding-protein.