We have previously shown that among several peptides encompassingvarious regions of theII-III loop of the dihydropyridine receptor
1 subunit,only one peptide corresponding to the Thr
671-Leu
690 region (designated as peptide A) activated ryanodinebinding to and induced calcium release fromthe sarcoplasmic reticulum [El-Hayek et al. (1995
) J. Biol.Chem.
270, 22116-22118]. To furtherlocalizewithin peptide A the minimum unit essential for activating thesarcoplasmic reticulum calcium releasechannel, we synthesized variously truncated forms of peptide A andexamined their ability to activateryanodine binding. We found that the carboxy-terminal 10-residueregion of peptide A encompassingArg
681-Leu
690 (peptide As-10; s, skeletalmuscle-type sequence) activated ryanodine binding in aRyR1-specific manner and induced calcium release even more efficiently thanthe 20-residue peptide A. Furthertruncation of one or more residue(s) of peptide As-10 virtuallyabolished both functions of activatingryanodine binding and inducing Ca
2+ release. Theactivating ability of As-10 seems to be determined byat least two factors: (1) the distribution of the positively chargedresidues, and (2) the skeletal muscle-type amino acid sequence, as deduced from the comparison of variouspeptides with modified structures.These results provide evidence that the minimum essential unit forthe
in situ trigger of skeletal muscleexcitation-contraction coupling is localized in theArg
681-Leu
690 region of the II-III loop ofthe
1 subunitof the dihydropyridine receptor.