Identification of calcium release-triggering and blocking regions of the II-III loop of the skeletal muscle dihydropyridine receptor.
In an attempt to identify and characterize functional domains of the rabbit skeletal muscle dihydropyridine receptor alpha 1 subunit II-III loop, we synthesized several peptides corresponding to different regions of the loop: peptides A, B, C, C1, C2, D (cf. Fig. 1). Peptide A (Thr671-Leu690) activated [3H]ryanodine binding to, and induced Ca2+ release from, rabbit skeletal muscle triads, but none of the other peptides had such effects. Peptide A-induced Ca2+ release and activation of ryanodine binding were partially suppressed by an equimolar concentration of peptide C (Glu724-Pro760) but were not affected by the other peptides. These results suggest that the short stretch in the II-III loop, Thr671-Leu690, is responsible for triggering SR Ca2+ release, while the other region, Glu724-Pro760, functions as a blocker of the release trigger. A hypothesis is proposed to account for how these subdomains interact with the sarcoplasmic reticulum Ca2+ release channel protein during excitation-contraction coupling.
el-Hayek
R
R
Boston Biomedical Research Institute, Massachusetts 02114, USA.
Antoniu
B
B
Wang
J
J
Hamilton
S L
SL
Ikemoto
N
N
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D020746:Calcium Channels, L-Type; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011817:Rabbits; D012433:Ryanodine / Q000378:metabolism; D015398:Signal Transduction
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D010455:Peptides; D012433:Ryanodine; D002118:Calcium