Abstract
The influence of luminal and cytoplasmic Ca2+ on the ability of ryanodine-sensitive stores to undergo multiple partial (“quantal”) releases has been assessed. Increased luminal Ca2+ levels do indeed modulate sarcoplasmic reticulum Ca2+ release by lowering the threshold agonist concentration required to elicit release, but the decrease in luminal Ca2+ that accompanies a partial release is not sufficient by itself to terminate release. Similarly, an increase in cytoplasmic Ca2+ lowers the threshold agonist concentration required to elicit release; thus, the bulk cytoplasmic Ca2+ levels attained during a release would only stimulate further release, not terminate it before it reached completion. Very high cytoplasmic Ca2+ levels (1–3 mm) also triggered release but were unable to terminate release before reaching completion. Thus, even the high local cytoplasmic Ca2+ concentration that might accompany release would also not terminate release. It is concluded that Ca2+ feedback can modulate release through ryanodine receptors but that it does not account for the properties of quantal release. The low affinity inhibitor tetracaine induces a decrease in the extent of release that cannot be explained solely by heterogeneous caffeine sensitivity of the stores. The results are interpreted in terms of a scheme that includes (i) heterogeneous sensitivity of stores, conferred in part by differences in luminal Ca2+ content and (ii) adaptive behavior on the part of individual ryanodine receptors.
Footnotes
- Received May 19, 1997.
- Accepted August 26, 1997.
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Send reprint requests to: Dr. Philip Palade, Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, TX 77555-0641. E-mail: philip.palade{at}utmb.edu
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This work was supported by National Institutes of Health Grant AR43200.
- The American Society for Pharmacology and Experimental Therapeutics
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