Open AccessCa 2+ /H + exchange, lumenal Ca 2+ release and Ca 2+ /ATP coupling ratios in the sarcoplasmic reticulum ATPase
Author(s) -
Inesi Giuseppe,
TadiniBuoninsegni Francesco
Publication year - 2014
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-013-0213-7
Subject(s) - serca , endoplasmic reticulum , biophysics , chemistry , cytosol , atp hydrolysis , intracellular , atpase , biochemistry , calcium pump , calcium , plasma membrane ca2+ atpase , enzyme , biology , organic chemistry
Abstract 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.