Ca2+-mediated potentiation of the swelling-induced taurine efflux from HeLa cells:: On the role of calmodulin and novel protein kinase C isoforms

The present work sets out to investigate how Ca2+ regulates the volume-sensitive taurine-release pathway in HeLa cells. Addition of Ca2+ - mobilizing agonists at the time of exposure to hypotonic NaCl medium augments the swelling-induced taurine release and subsequently accelerates the inactivation of the release pathway. The accelerated inactivation is not observed in hypotonic Ca2+ - free or high-K media. Addition of Ca2+ -mobilizing agonists also accelerates the regulatory volume decrease, which probably reflects activation of Ca2+ - activated K channels. The taurine release from control cells and cells exposed to Ca2+ agonists is equally affected by changes in cell volume, application of DIDS and arachidonic acid, indicating that the volume-sensitive taurine leak pathway mediates the Ca2+ -augmented taurine release. Exposure to Ca2+ -mobilizing agonists prior to a hypotonic challenge also augments a subsequent swelling-induced taurine release even though the intracellular Ca2+ - concentration has returned to the unstimulated level. The Ca2+ -induced augmentation of the swelling-induced taurine release is abolished by inhibition of calmodulin, but unaffected by inhibition of calmodulin-dependent kinase II, myosin light chain kinase and calcineurin. The effect of Ca2+ -mobilizing agonists is mimicked by protein kinase C (PKC) activation and abolished in the presence of the PKC inhibitor Go6850 and following downregulation of phorbol ester-sensitive PKC isoforms. It is suggested that Ca2+ regulates the volume-sensitive taurine-release pathway through activation of calmodulin and PKC isoforms belonging to the novel subclass (nPKC).