AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 270: H678-H684, 1996;
0363-6135/96 $5.00
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AJP - Heart and Circulatory Physiology, Vol 270, Issue 2 678-H684, Copyright © 1996 by American Physiological Society

ARTICLES

Cholinergic stimulation modulates negative inotropic effect of cocaine on ferret ventricular myocardium

L. Miao, Z. Qiu and J. P. Morgan
Charles A. Dana Research Institute, Boston, Massachusetts, USA.

We tested the hypothesis that the negative inotropic effect (NIE) of cocaine is mediated, at least in part, by cholinergic stimulation and can be correlated with the degree of adenosine 3',5'-cyclic monophosphate (cAMP) dependency of the inotropic state. Cardiac myocytes were isolated from left ventricles of ferrets and loaded with the fluorescent Ca2+ indicator indo 1. Cells were placed in physiological solution containing 2.0 mM Ca2+ and stimulated at 0.5 Hz and 30 degrees C. Cocaine decreased peak cell shortening and peak intracellular Ca2+ in a concentration-dependent manner (10(-8)-10(-4) M). The concentration-response curve of cocaine was shifted significantly downward compared with those of lidocaine and procaine in the same range of concentrations. Atropine (10(-6) M) shifted the concentration-response curve of cocaine, but not those of lidocaine and procaine, rightward, with a pA2 value (7.66) similar to that obtained with carbachol (7.99). With prior addition of isoproterenol (ISO, 10(-8) M) or increased Ca2+ (4.0 mM) to increase cell shortening to the same degree (approximately 60%), cocaine and carbachol decreased contractility to a significantly greater extent in ISO-stimulated myocytes. To clarify whether these treatments changed responsiveness of the contractile elements to Ca2+, the effect of 2,3-butanedione monoxime, an agent that interferes with the interaction of myosin and actin, was tested with previous addition of ISO or increased Ca2+, and no differential effect occurred. Therefore, we postulate that 1) the NIE of cocaine on myocytes is caused by decreased Ca2+ availability; 2) this effect is due to specific stimulation of cholinergic receptors in addition to other direct myocardial (probably local anesthetic) effects; and 3) the NIE correlates with the level of cAMP dependence of the inotropic state.


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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. M. Knuepfer and Q. Gan
Role of cholinergic receptors and cholinesterase activity in hemodynamic responses to cocaine in conscious rats
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1999; 276(1): R103 - R112.
[Abstract] [Full Text] [PDF]


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