The quantal nature of calcium release to caffeine in single smooth muscle cells results from activation of the sarcoplasmic reticulum Ca(2+)-ATPase

UMMS Affiliation

Department of Physiology

Publication Date


Document Type



Adenosine Triphosphate; Animals; Bufo marinus; Caffeine; Calcium; Calcium Channels; Calcium-Transporting ATPases; Cell Compartmentation; Cell Membrane Permeability; Cells, Cultured; Detergents; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Ion Channel Gating; Muscle Proteins; Muscle, Smooth; Ryanodine Receptor Calcium Release Channel; Saponins; Sarcoplasmic Reticulum; Terpenes; Thapsigargin


Life Sciences | Medicine and Health Sciences


Calcium release from intracellular stores occurs in a graded manner in response to increasing concentrations of either inositol 1,4,5-trisphosphate or caffeine. To investigate the mechanism responsible for this quantal release phenomenon, [Ca2+] changes inside intracellular stores in isolated single smooth muscle cells were monitored with mag-fura 2. Following permeabilization with saponin or alpha-toxin the dye, loaded via its acetoxymethyl ester, was predominantly trapped in the sarcoplasmic reticulum (SR). Low caffeine concentrations in the absence of ATP induced only partial Ca2+ release; however, after inhibiting the calcium pump with thapsigargin the same stimulus released twice as much Ca2+. When the SR Ca(2+)-ATPase was rendered non-functional by depleting its "ATP pool," submaximal caffeine doses almost fully emptied the stores of Ca2+. We conclude that quantal release of Ca2+ in response to caffeine in these smooth muscle cells is largely due to the activity of the SR Ca(2+)-ATPase, which appears to return a portion of the released Ca2+ back to the SR, even in the absence of ATP. Apparently the SR Ca(2+)-ATPase is fueled by ATP, which is either compartmentalized or bound to the SR.

DOI of Published Version



J Biol Chem. 1996 Jan 26;271(4):1821-4.

Journal/Book/Conference Title

The Journal of biological chemistry

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PubMed ID