Potentiating effect of acetylcholine on stimulation by isoproterenol of L-type Ca2+ current and arrhythmogenic triggered activity in guinea pig ventricular myocytes.
BACKGROUND
The objective of this study was to determine whether the effect of isoproterenol (Iso) to increase L-type Ca2+ current [I(Ca(L))] and action potential duration (APD) was potentiated in ventricular myocytes following termination of an exposure of these cells to acetylcholine (ACh), and whether this potentiating effect of ACh could be arrhythmogenic.


RESULTS
Transmembrane currents and potentials of guinea pig isolated ventricular myocytes were measured using the whole cell, patch clamp technique. Stimulation of I(Ca(L)) and prolongation of APD caused by Iso (10 nmol/L) were attenuated in the presence of ACh (10 micromol/L), but were transiently enhanced by 111% +/- 20% and 214% +/- 44%, respectively, following termination of a 2- to 4-minute exposure of myocytes to ACh. No changes were observed in the absence of Iso. Both the amplitude and incidence of Iso-induced transient inward current, afterdepolarizations, and sustained triggered activity were greater immediately after termination of exposure to ACh than before application of ACh.


CONCLUSIONS
Stimulation by Iso of I(Ca(L)) is transiently enhanced in guinea pig ventricular myocytes following termination of exposure of these cells to ACh. The rebound increase of Iso-stimulated I(Ca(L)) is associated with an increase of APD and induction of arrhythmogenic triggered activity.
Song
Y
Y
Department of Medicine, University of Florida Medical School, Gainesville 32610-0277, USA.
Shryock
J C
JC
Belardinelli
L
L
D000109:Acetylcholine / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D011950:Receptors, Cholinergic; D007545:Isoproterenol; D000109:Acetylcholine