Ca2+-dependent dual functions of peptide C. The peptide corresponding to the Glu724-Pro760 region (the so-called determinant of excitation-contraction coupling) of the dihydropyridine receptor alpha 1 subunit II-III loop.
Both in vivo and in vitro studies suggest that the Glu(724)-Pro(760) (peptide C) region of the dihydropyridine receptor alpha1 II-III loop is important for excitation-contraction coupling, although its actual function has not yet been elucidated. According to our recent studies, peptide C inhibits Ca(2+) release induced by T-tubule depolarization or peptide A. Here we report that peptide C has Ca(2+)-dependent dual functions on the skeletal muscle ryanodine receptor. Thus, at above-threshold [Ca(2+)]s (> or =0.1 microm) peptide C blocked peptide A-induced activation of the ryanodine receptor (ryanodine binding and Ca(2+) release); peptide C also blocked T-tubule depolarization-induced Ca(2+) release. However, at sub-threshold [Ca(2+)]s (<0.1 microm), peptide C enhanced ryanodine binding and induced Ca(2+) release. If peptide A was present, together with peptide C, both peptides produced additive activation effects. Neither peptide A nor peptide C produced any appreciable effect on the cardiac muscle ryanodine receptor at both high (1.0 microm) and low (0.01 microm) Ca(2+) concentrations. These results suggest the possibility that the in vivo counterpart of peptide C retains both activating and blocking functions of the skeletal muscle-type excitation-contraction coupling.
Yamamoto
Takeshi
T
Boston Biomedical Research Institute, Watertown, Massachusetts 02472, USA.
Rodriguez
John
J
Ikemoto
Noriaki
N
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry*; D002154:Calpain / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011107:Polylysine / Q000494:pharmacology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011817:Rabbits; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D020746:Calcium Channels, L-Type; D003374:Coumarins; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D011107:Polylysine; D002110:Caffeine; C030123:coumarin; D002154:Calpain; D002118:Calcium