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 synthetized several peptides corresponding to different regions of the loop: peptides A, B, C, C1, C2, D (cf. Pig, 1). Peptide A (Thr(671)- Leu(690)) activated [H-3]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 (Glu(724)-Pro(760)) but were not affected by the other peptides. These results suggest that the short stretch in the II-III loop, Thr(671)-Leu(690), is responsible for triggering SR Ca2+ release, while the other region, Glu(724)-Pro(760), 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.