Mechanisms underlying varioux regulation of Ca chammel activity in smooty muscle cells

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This project was undertaken to elucidate the mechanisms underlying variety oof regulation of Ca channel activity in smooth muscle cells. In previous study, we showed that norepinephrine (NE) reduces Ca current via two distinctive mechanisms ; Ca-dependent inactivation of Ca channels and Ca-independent regulation. In the present study, it was found that Ca-dependent inactivation of Ca channels mechanism in response to NE was much less available in ureter smooth muscle cells than in vas deferens in Ca-independent mechanism in two type of cells may be attributable to NE-induced release of arachidonic acid (AA) which may contribute the reduction of Ca current in cells from vas deferens but not from ureter. Although the decrease in Ca current by exogenously applied AA was large in vas deferens cells, it was not clear that the release of AA contributed to the NE-induced decrease in Ca current. The AA-induced decrease in Ca current was not affected by treatment with inhibitors of cycloxygenas … More e and lipoxygenase. The decrease was. however, partly inhibited by superoxide desmutase, indicating involvement of superoxide anion production from AA.Moreover, it became clear that NE reduced Ca-activated K current more extensively than Ca current. This resulted in the prolongation of action potentiol duration and the potentiation of contraction.The possibility was also examined that the Ca channel activity is increased by significant decrease in atored Ca in the cell after large release. It was found that memvrane excitability was increased and action potentials were more frequently generated after treatment with cyclopiazonic acid which is a novel inhibitor of Ca-pump in sarcoplasmic reticulum. The major mechanism for the CPA-induced change was the inhibition of Ca-activated K current. Although direct evidence indication ghat depletion of intracellular Ca storage sites results in the potentiation of Ca channel activity was not obtained, the possibility is also likely and may contribute to the increase in membrane excitabilyty. Less