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Journal of Pharmacology And Experimental Therapeutics, Vol. 169, Issue 2, 308-314, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics

THE EFFECT OF METHYLXANTHINES AND LOCAL ANESTHETICS ON FRAGMENTED SARCOPLASMIC ETICULUM

PHILIP N. JOHNSON 1 and G. INESI 1

1 Cardiovascular Research Institute, University of California; Department of Physiology, University of the Pacific, San Francisco, California

Net Ca++ accumulation by fragmented sarcoplasmic reticulum is the resultant of active Ca++ uptake and passive Ca++ outflow. These two processes were separately measured and differentially altered by a stepwise heat denaturation and by pharmacologic agents. Methylxanthines reduce net Ca++ accumulation by increasing membrane permeability and Ca++ outflow from loaded vesicles. Local anesthetics at low concentrations (<1 mM) decrease membrane permeability and Ca++ diffusion across the membrane. The latter effect is manifested as inhibition of passive Ca++ outflow from loaded vesicles, slight impairment of Ca++ uptake (a diffusion step in the mechanism of active uptake being implied), noncompetitive inhibition of adenosine triphosphate-independent Ca++ binding to the membranes and prevention of the effect of methyixanthines on Ca++ outflow from loaded vesicles. At higher concentrations (> 1 mM), local anesthetics increase Ca++ outflow and totally prevent accumulation. Veratridine ( 10-6-10-2 M) has no effect on Ca++ uptake by sarcoplasmic reticulum.

Submitted on March 3, 1969
Accepted on June 18, 1969




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