Regulation by acetylcholine of ca current in rabbit atrioventricular (av) node cells. Habuchi, Yoshizumi, Manabu Nishio, Hideo Tanaka, Taku Yamamoto, Ling -Ling Lu, and Manabu Yoshimura. Departments of Laboratory Medicine and Internal Medicine III, Kyoto Prefectural University of Medicine, Kawaramachi, Kamigyo-ku, Kyoto 602, Japan
APStracts 3:0255H, 1996.
Effects of acetylcholine (ACh) on the L-type Ca2+ current (ICa) were examined on the isolated atrioventricular (AV) node cells exhibiting spontaneous contractions and the pacemaker current, If. ACh at a saturating concentration of 10 [mu]M reduced basal ICa by 48 +/-6 %. The ACh effect was abolished by dialysis with 8Br cAMP, a cAMP- dependent protein kinase inhibitor, or GDP[beta]S. Neither dialysis with cGMP or L-NMMA nor application of the cGMP-dependent protein kinase inhibitor KT5823 (1 [mu]M) affected the ACh inhibition of ICa. Nitric oxide donor SIN-1 (100 [mu]M) and type III phosphodiesterase (PDE) inhibitor trequinsin (10 nM) enhanced basal ICa by 10-20 %, while type IV PDE inhibitor RO20-1724 (30 [mu]M) caused a large ICa stimulation comparable to IBMX. These findings indicate that ACh inhibits basal ICa primarily by suppressing cAMP synthesis, and that these cells have a potent type IV (cGMP- independent) PDE activity to determine the basal cAMP concentration. When ICa was stimulated by IBMX (100 [mu]M), the inhibitory effect of ACh was slightly reduced by L- NMMA, cGMP and methylene blue, but not by KT5823 or RO20-1724. ACh hardly inhibited, or rather enhanced, IBMX-stimulated ICa when forskolin (3 [mu]M) was co- applied or the IBMX concentration was increased to 500 [mu]M. These findings suggest that cAMP is degraded in the presence of 100 [mu]M IBMX to some extent, and that RO20- 1724-insensitive PDEs including in part type II PDE, for which IBMX has a relatively high Ki, contribute to the cAMP degradation. 

Received 20 Setember 1995; accepted in final form 22 May 1996.
APS Manuscript Number H890-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96