Abstract
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.
Footnotes
- Received March 3, 1969.
- Accepted June 18, 1969.
- © 1969, by The Williams & Wilkins Co.
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