YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Regulation of Atrial $Ca^{2+}$ Signaling by Inositol 1,4,5-Trisphosphate Receptor and Mitochondria

이노시톨 삼인산 수용체와 미토콘드리아에 의한 심방 근세포 $Ca^{2+}$ 신호전달의 조절

  • Lee , Hyang-Jin (College of Pharmacy, Chungnam National University) ;
  • Cleemann , Lars (Department of Pharmacology, Georgetown University Medical Center) ;
  • Morad , Martin (Department of Pharmacology, Georgetown University Medical Center) ;
  • Woo, Sun-Hee (College of Pharmacy, Chungnam National University)
  • Published : 2004.01.01
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Abstract

Atrial myocytes have two functionally separate groups of ryanodine receptors (RyRs): those at the periphery colocalized with L-type $Ca^{2+}$channels (DHPRS) and those a t the cell interior not associated with DHPRs. $Ca^{2+}$ current ($I_{ca}$) directly gates peripheral RyRs on action potential and the subsequent peripheral $Ca^{2+}$ release propagates into the center of atrial myocytes. The mechanisms that regulate the $Ca^{2+}$+ propagation wave remain Poorly understood. Using 2-D confocal$Ca^{2+}$ imaging, we examined the role of inositol 1,4,5-trisphosphate receptor (IP $_3R$) and mitochondria on ($I_{ca}$)- gated local $Ca^{2+}$ signaling in rat atrial myocytes. Blockade of IP $_3R$ by xestospongin C (XeC) partially suppressed the magnitudes of I ca-gated central and peripheral $Ca^{2+}$ releases with no effect on $I_{ca}$. Mitochondrial staining revealed that mitochondria were aligned with ${\thickapprox}2-{\mu}m$ separations in the entire cytoplasm of ventricular and atrial myocytes. Membrane depolarization induced rapid mitochondrial $Ca^{2+}$ rise and decay in the cell periphery with slower rise in the center, suggesting that mitochondria may immediately uptake cytosolic $Ca^{2+}$, 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 $Ca^{2+}$ handing on action potential may serve as a cofactor for the $Ca^{2+}$ propagation from the DHPR-coupled RyRs to the DHPR-uncoupled RyRs with large gaps between them.

Keywords

References

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