Ca2+/H+ exchange, lumenal Ca2+ release and Ca2+/ATP coupling ratios in the sarcoplasmic reticulum ATPase

Autor: Giuseppe Inesi, Francesco Tadini-Buoninsegni
Rok vydání: 2013
Předmět:
Zdroj: Journal of Cell Communication and Signaling
ISSN: 1873-961X
1873-9601
DOI: 10.1007/s12079-013-0213-7
Popis: The Ca(2+) transport ATPase (SERCA) of sarcoplasmic reticulum (SR) plays an important role in muscle cytosolic signaling, as it stores Ca(2+) in intracellular membrane bound compartments, thereby lowering cytosolic Ca(2+) to induce relaxation. The stored Ca(2+) is in turn released upon membrane excitation to trigger muscle contraction. SERCA is activated by high affinity binding of cytosolic Ca(2+), whereupon ATP is utilized by formation of a phosphoenzyme intermediate, which undergoes protein conformational transitions yielding reduced affinity and vectorial translocation of bound Ca(2+). We review here biochemical and biophysical evidence demonstrating that release of bound Ca(2+) into the lumen of SR requires Ca(2+)/H(+) exchange at the low affinity Ca(2+) sites. Rise of lumenal Ca(2+) above its dissociation constant from low affinity sites, or reduction of the H(+) concentration by high pH, prevent Ca(2+)/H(+) exchange. Under these conditions Ca(2+) release into the lumen of SR is bypassed, and hydrolytic cleavage of phosphoenzyme may yield uncoupled ATPase cycles. We clarify how such Ca(2+)pump slippage does not occur within the time length of muscle twitches, but under special conditions and in special cells may contribute to thermogenesis.
Databáze: OpenAIRE
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