Simultaneous effects of carbachol on intracellular Na+ activity, action potential, and twitch tension in guinea-pig cardiac ventricular papillary muscles.
Effects of carbachol (CCh) on the twitch tension, intracellular Na+ activity (aNai), and action potential were simultaneously measured in guinea-pig cardiac ventricular papillary muscles. In fibers driven at 60 beats/min, 100 microM CCh significantly increased the twitch tension and aNai, and decreased the action potential duration at 30 and 90% repolarization (APD30 and APD90) without changing the maximum rate of the rise of the upstroke (Vmax). Staurosporine (1 microM) alone gradually decreased the twitch tension and aNai without changing the action potential. In the presence of staurosporine, the administration of CCh restored aNai and caused the same changes in twitch tension and APD shortening with no effect on Vmax. Pretreatment with 1 microM atropine completely eliminated the effects of 100 microM CCh. Cesium (20 mM) depolarized the cell membrane and significantly increased the twitch tension and APD90 with decreases in the Vmax and aNai. CCh (100 microM) in the presence of 20 mM Cs+ biphasically decreased and increased the twitch tension and significantly decreased the Vmax and aNai with an increase in the APD90. The results suggest that the muscarinic receptor-mediated increase of aNai is protein kinase C-independent. The aNai increase is associated with the positive inotropic effect and the abbreviation of the action potential duration. In addition to the increase in aNai, the increase of the myofibrillar calcium sensitivity involved is responsible for the positive inotropic effect which is still evident after the sodium influx is inhibited by Cs+.
Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC.
J M
JM
Yang
K T
KT
Chung
C I
CI
Lin
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002586:Cesium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D002586:Cesium; D001285:Atropine; D002217:Carbachol; D012964:Sodium; D019311:Staurosporine