| Research Abstract |
Presence of store-operated and/or ligand-operated Ca^<2+> influx pathways have been indicated in many kinds of cells and their important roles in Ca^<2+> homeostasis were reported. On the other hands, in many excitable cells including cardiac and skeletal muscles, voltage-dependent Ca^<2+> channel (VDCC) have been thought to be the major Ca^<2+> influx pathway. However, we recently showed the presence of SOC pathway in skeletal muscle, where the SOC activity was much higher than that of VDCC. We also found that non-VDCC pathway was also present in rat and guinea pig ventricular muscle. We examined properties of the pathway by observing Ca^<2+> dynamics using laser-scanning confocal microscope or evanescent-field microscope and determining SR Ca^<2+> content with Rapid Cooling Contracture (RCC) method. The influx showed marked temperature-dependence. Because the influx was resistant to nifidipine or KB-R7943, the possibility of DHPR or Na^+/Ca^<2+> exchanger was excluded. Among putative inhibitors of various Ca^<2+> influxes, neither 2-aminoethoxydiphenyl borate (2-APB) nor SKF96365 was significantly effective. Interestingly, it was suppressed to a half by 20 μM econazole, a putative inhibitor to TRPV5. With RT-PCR analysis, mRNA for TRPV6, but not for TRPV5, was detected in ventricular muscles, suggesting that TRPV6 may be a candidate for the Ca^<2+> influx pathway. On the contrary, the SOC Ca^<2+> influx in skeletal muscle was very sensitive to 2-APB but not to econazole. These results suggest that molecules for the non-VDCC pathways should be different in cardiac and skeletal muscles. Further studies are required for the localization and identification of the pathways.
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