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Buffering Contribution of Mitochondria to the $[Ca^{2+}]_i$ Increase by $Ca^{2+}$ Influx through Background Nonselective Cation Channels in Rabbit Aortic Endothelial Cells

Kim, Young-Chul    (Department of Physiology, Chungbuk National University, College of Medicine   ); Lee, Sang-Jin    (Department of Physiology, Chungbuk National University, College of Medicine   ); Kim, Ki-Whan    (Department of Physiology and Biophysics, Seoul National University College of Medicine  );
  • 초록

    To prove the buffering contribution of mitochondria to the increase of intracellular $Ca^{2+}$ level ( $[Ca^{2+}]_i$ ) via background nonselective cation channel (background NSCC), we examined whether inhibition of mitochondria by protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) affects endothelial $Ca^{2+}$ entry and $Ca^{2+}$ buffering in freshly isolated rabbit aortic endothelial cells (RAECs). The ratio of fluorescence by fura-2 AM ( $R_{340/380}$ ) was measured in RAECs. Biological state was checked by application of acetylcholine (ACh) and ACh ( $10{\mu}M$ ) increased $R_{340/380}$ by $1.1{\pm}0.15$ ( $mean{\pm}S.E.$ , n=6). When the external $Na^+$ was totally replaced by $NMDG^+$ , $R_{340/380}$ was increased by $1.19{\pm}0.17$ in a reversible manner (n=27). $NMDG^+$ -induced $[Ca^{2+}]_i$ increase was followed by oscillatory decay after $[Ca^{2+}]_i$ reached the peak level. The increase of $[Ca^{2+}]_i$ by $NMDG^+$ was completely suppressed by replacement with $Cs^+$ . When $1{\mu}M$ CCCP was applied to bath solution, the ratio of $[Ca^{2+}]_i$ was increased by $0.4{\pm}0.06$ (n=31). When $1{\mu}M$ CCCP was used for pretreatment before application of $NMDG^+$ , oscillatory decay of $[Ca^{2+}]_i$ by $NMDG^+$ was significantly inhibited compared to the control (p<0.05). In addition, $NMDG^+-induced$ increase of $[Ca^{2+}]_i$ was highly enhanced by pretreatment with $2{\mu}M$ CCCP by $320{\pm}93.7$ %, compared to the control ( $mean{\pm}S.E.$ , n=12). From these results, it is concluded that mitochondria might have buffering contribution to the $[Ca^{2+}]_i$ increase through regulation of the background NSCC in RAECs.


  • 주제어

    Endothelial cell .   Intracellular $Ca^{2+}$ concentration .   Nonselective cation channel .   Mitochondria.  

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