It was reported that a lack of Mitsugumin29 (MG29), a protein expressed at the triad junction, caused morphological changes in sarcoplasmic reticulum and T-tubules, reduced twitch/tetanus ratio, and increased susceptibility to fatigue in adult skeletal muscle and dysfunction of store-operated Ca2+ entry (SOC) in embryonic and neonatal muscles. To deepen our understanding of the role of MG29 in the Ca2+ handling in adult skeletal muscle, Ca2+ stores of wild-type and mutant muscle fibers were depleted by repetitive high-K+ treatments in a Ca2+-free medium. Although wild-type muscle showed only minor caffeine contracture after high-K+ response had disappeared, the mutant muscle showed remarkable caffeine contracture under the conditions used, suggesting functional compartmentalization of the Ca2+-store in the mutant. Activation of SOC in adult mutant muscle was observed upon the voltage-sensitive store depletion as is true with the wild-type muscle. Thus MG29 is not involved in the SOC activation at variance with the previous conclusion with immature muscles. (C) 2003 Elsevier Inc. All rights reserved.