Depression by carbachol of calcium-dependent action potentials in the canine ventricular muscle depolarized by potassium.
Effects of carbachol on the Ca2+-dependent action potentials were investigated in the canine ventricular muscle which was depolarized and made inexcitable by elevation of the extracellular concentration of K+ ([K+]0) to 30 mM. Regenerative action potentials ("the slow response") were induced by electrical stimulation at low frequency with high intensity (0.1 Hz, 5 msec duration and 5 mA). The amplitude of the slow response varied 31 mV for a tenfold change in [Ca2+]0. The amplitude and duration of the slow response were increased by isoproterenol (10(-7) M) and were decreased by carbachol (3 X 10(-6) M). The actions of carbachol on the slow response were antagonized by atropine (10(-6) M). Propranolol (3 X 10(-7) M) decreased the amplitude and duration of the slow response. In the presence of propranolol, carbachol (3 X 10(-6) M) produced a further decrease in the amplitude and duration of the slow response. These results suggest that electrical stimulation induces the slow response which is augmented by catecholamines released from the adrenergic nerve endings in response to the stimulation and/or K+-depolarization. Carbachol depresses the slow response by its muscarinic action which may involve both "indirect" and "direct" effects, the former being the effect caused by counteracting the catecholamine-induced augmentation of the slow response and the latter, the effect irrespective of catecholamines.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology*; D002395:Catecholamines / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012038:Regeneration; D016276:Ventricular Function
D002395:Catecholamines; D002217:Carbachol; D011433:Propranolol; D011188:Potassium; D002118:Calcium