EFFECTS OF NEUROENDOCRINAL FACTORS ON CARDIAC SODIUM-CALCIUM EXCHANGER

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1) As neuroendocrine factors, we tested effects on Na^+/Ca^<2+> exchange current (I_<NCX>) of angiotensin II, endothelin, epinephrine and phenylephrine with the whole cell voltage clamp method using single guinea-pig cardiac ventricular cells. However, none of them exerted effects on Na-Ca exchange current (I_<NCX>)2) Butanedione monoxime (BDM) is called a chemical phosphatase. We found that BDM inhibited I_<NCX>. We tested whether the effect of BDM was due to dephosphorylation of NCX. Activation of A-kinase and C kinase did not affect NCX. NCX1 mutants with possible phosphorylation site serines replaced by alanines were also inhibited by BDM. Therefore we concluded that phosphorylation and dephosphorylation mechanisms are not involved in the inhibitory effects of BDM on NCX.3) Interaction of NCX with Na-H exchange was investigated by measuring the reversal potential (E_<NCX>) of I_<NCX> before and after acidification to pH4.9 from pH7.4. E_<NCX> shifted in the negative direction by acidification. The negative shift was inhibited by inhibitors of Na-H exchanger and enhanced by Na-H exchange accelerator. Addition of Na-H exchange inhibitor only during the recovery from acidification also prevented shift in E_<NCX>, indicating that Na-H exchange was inhibited by acid. These results suggest that Na-H exchange and Na-Ca exchange are closely linked to each other. Increase in Na_I increased during recovery from acidification was calculated to be about 3 mM.