Ca2+ feedback on "quantal" Ca2+ release involving ryanodine receptors.
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.
Dettbarn
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Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555-0641, USA.
Palade
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D005246:Feedback; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D002118:Calcium