Function and regulatory mechonismes of ionic chapnels in vasculer snoock muscle cells University of Tokyo

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1) To clarify the significance and characterization of Ca^<2+> -permeable nonselective cation channels activated by vasopressin and endothelin-1 (receptor-mediated non-selective cation channels) in vascular smooth muscle cells, the patch clamp techniques, Ca^<2+> or tension measurement were applied in aortic smooth muscle cells. The results suggested that calcium ectry and membrane depolarization elicited by these agonists are partly mediated by a receptormediated Ca^<2+> -permeable non-selective cation channel in vascular smooth muscle cells. Also, we showed the characteristics and activation mechanisms of the channel. Furthermore, we investigated the effects of extracellular Mg^<2+> and omega-3 polyunsaturated fatty acids, which are known to produce vascular relaxation or hypotensive effects, on the receptor-mediated non-selective cation channels. We showed that extracellular Mg^<2+> and omega-3 polyunsaturated fatty acids effectively inhibit receptor-mediated non-selective cation channel. which may play an important role in the regulation of vascular tone.2) In tracheal myocytes, to investigate the activation mechanism and characterization of Ca^<2+> -dependent Cl^- current, the patch clamp technique was applied. We presented that Ca^<2+> -dependent Cl^- current can be activated by SR (sarcoplasmic reticulum) Ca^<2+> release due to neurokinin A or caffeine (through IP_3 or ryanodine receptors) as well as by Ca^<2+> infulx due to the voltage-dependent L-type Ca^<2+> current. It also showed that the functional coupling of ryanodine receptor to the voltage-dependent L-type Ca^<2+> channels exists in tracheal smooth muscle cells.