Effects of calcium, calmodulin, protein kinase C and protein tyrosine kinases on volume-activated taurine efflux in human erythroleukemia cells

The effects of calcium, calmodulin, protein kinase C (PKC) and protein tyro sine kinase (PTK) modulators were examined on the volume-activated taurine efflux in the erythroleukemia cell line K562. Exposure to hypoosmotic solut ion significantly increased taurine efflux and intracellular calcium concen tration ([Ca2+](i)). The Ca2+ channel blockers La3+ (1 mM), verapamil (200 muM) and nifedipine (100 muM) inhibited the hypoosmotically-induced [Ca2+]( i) increase by more than 90%, while the volume-activated taurine efflux was inhibited by 61.3 +/- 9.5, 74.1 +/- 9.3 and 38.0 +/- 1.5%, respectively. F urthermore, the calmodulin inhibitors W7 (50 muM) and trifluoperazine (110 muM) and the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62 (2 muM) significantly blocked the volume-activated taurine efflux by 93.4 +/- 2.7, 77.9 +/- 3.5 and 61.3 +/- 15.8%, respectively. In contrast, the PKC i nhibitor staurosporine (200 nM) or the PKC activator phorbol 12-myristate 1 3-acetate (100 nM) did not have significant effects on the volume-activated taurine efflux. However, pretreatment with PTK inhibitors genistein, tyrph ostin A25, and tyrphostin A47 blocked the volume-activated taurine efflux. These results suggest that the volume-activated taurine efflux in K562 cell s may not directly involve Ca2+, but may require the presence of calmodulin and/or PTK. (C) 2001 Wiley-Liss, Inc.