Control of intracellular ionized calcium concentration by sarcolemmal and intracellular mechanisms.
The regulation of the resting intracellular ionized calcium concentration [( Ca2+]i) has been studied in ferret papillary muscle using the photoprotein aequorin to measure [Ca2+]i. Elevating [Ca2+]o produced an initial rapid increase of [Ca2+]i and tension which then decayed to a steady level. This secondary fall of [Ca2+]i is attributed to a secondary decrease of Ca entry on Na-Ca exchange produced by the known fall of [Na+]i. Replacing external Na by K produced a large transient increase of both [Ca2+]i and tension which then decayed spontaneously to near the resting level. If Na was removed after metabolic inhibition with cyanide and deoxyglucose then neither tension nor [Ca2+]i recovered. The addition of the mitochondrial uncoupler FCCP to a muscle in Na-free solution produced a gradual rise of tension but only elevated [Ca2+]i after a delay of many minutes. Similarly caffeine did not elevate [Ca2+]i. These experiments do not support the hypothesis that the regulation of resting [Ca2+]i in Na-free solutions depends solely on intracellular sequestration of [Ca2+]i. The first twitch elicited in Na-containing solutions after exposure to Na-free solution was much larger than control and was associated with a large Ca transient attributed to increased loading of the sarcoplasmic reticulum with Ca in the Na-free solution. The elevation of [Ca2+]i in Na-free solutions was accompanied by spontaneous fluctuations of both [Ca2+]i and tension with a frequency of about 3 Hz. These fluctuations were abolished by drugs such as caffeine or ryanodine which interfere with sarcoplasmic reticulum function. These results provide direct evidence for the spontaneous release of Ca from the sarcoplasmic reticulum inferred from previous, less direct, work.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005289:Ferrets; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009940:Organoids / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D000963:Antimetabolites; D012964:Sodium; D002118:Calcium