褐色脂肪細胞でのベータ作用によるミトコンドリアと滑面小胞体からのカルシウム遊離と細胞膜でのカルシウム流入の活性化

抄録

In brown adipocytes, α1 adrenoceptor activation elicits IP3-induced Ca²⁺ release and store-operated Ca²⁺ entry (SOC) from the ER, while β3-receptor activity activates lipolysis and uncoupling proteins in mitochondria, producing heat. Uncoupling of mitochondrial respiration by FCCP activates mitochondrial Ca²⁺ release, non-SOC Ca²⁺ entry, Ca²⁺ release from the ER and SOC. How this mitochondria-ER-plasmalemma Ca²⁺ coupling is regulated by an endogenous activator, we have measured Ca²⁺ in the ER ([Ca²⁺]ER) using cameleon expressed in the ER as well as intracellular Ca²⁺ ([Ca²⁺]i) and mitochondrial potential. The first phase of isoprotelenol-induced rises in [Ca²⁺]i was accompanied by mitochondrial depolarization. The second phase was paralleled by mitochondrial repolarization, accompanied by a rise in intracellular Mg2+ and partially blocked by removing external Ca²⁺ and fully by oligomycin. The second and third phases were blocked by removing external Ca²⁺ and U73122. FCCP as well as cyclopiazonic acid (CPA) transiently reduced [Ca²⁺]ER. Likewise, isoprotelenol decreased [Ca²⁺]ER for a period much longer than those by FCCP and CPA. Thus, β3-receptor activation causes uncoupling of mitochondrial respiration that depolarizes the mitochondrial membrane, releases Ca²⁺, activates uncoupling-associated non-SOC Ca²⁺ entry and activates Ca²⁺ release from the ER via activation of phospholipase C and subsequently SOC. [J Physiol Sci. 2007;57 Suppl:S131]