이노시톨 삼인산 수용체와 미토콘드리아에 의한 심방 근세포 Ca2+ 신호전달의 조절

Regulation of Atrial Ca2+ Signaling by Inositol 1,4,5-Trisphosphate Receptor and Mitochondria

Atrial myocytes have two functionally separate groups of ryanodine receptors (RyRs): those at the periphery colocalized with L-type Ca2+channels (DHPRS) and those at the cell interior not associated with DHPRs. Ca2+ current (1Ca) directly gates peripheral RyRs on action potential and the subsequent peripheral Ca2+ release propagates into the center of atrial myocytes. The mechanisms that regulate the Ca2+ propagation wave remain Poorly understood. Using 2-D confocal Ca2+ imaging, we examined the role of inositol 1,4,5-trisphosphate receptor (IP 3R) and mitochondria on Ica- gated local Ca2+ signaling in rat atrial myocytes. Blockade of IP3R by xestospongin C (XeC) partially suppressed the magnitudes of I ca-gated central and peripheral Ca2+ releases with no effect on Ica-. Mitochondrial staining revealed that mitochondria were aligned with ?2-㎛ separations in the entire cytoplasm of ventricular and atrial myocytes. Membrane depolarization induced rapid mitochondrial Ca2+ rise and decay in the cell periphery with slower rise in the center, suggesting that mitochondria may immediately uptake cytosolic Ca2+, released from the peripheral SR on depolarization, and re-release the Ca 2+ into the cytosol to activate neighboring central RyRs. Our data suggest that the activation of IP 3R and mitochondrial Ca2+ handing on action potential may serve as a cofactor for the Ca2+ propagation from the DHPR-coupled RyRs to the DHPR-uncoupled RyRs with large gaps between them.