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.
Habuchi
Y
Y
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan. yhabuchi@koto.kpu-m.ac.jp
Tanaka
H
H
Yamamoto
T
T
Nishio
M
M
Morikawa
J
J
Yoshimura
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001283:Atrioventricular Node / Q000166:cytology* / Q000187:drug effects; D015220:Calcium Channels / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012849:Sinoatrial Node / Q000378:metabolism* / Q000502:physiology
D015220:Calcium Channels; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine