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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Activation of maxi-anion channel by protein tyrosine dephosphorylation

¹Department of Cell Physiology, National Institute for Physiological Sciences, ²Department of Physiological Sciences, School of Life Science, Graduate University for Advanced Studies (SOKENDAI), and ³Division of Molecular Neurobiology, National Institute for Basic Biology, Okazaki, Japan; ⁴Laboratory of Molecular Physiology, Institute of Physiology and Biophysics, Academy of Sciences and Department of Biophysics, National University, Tashkent, Uzbekistan; and ⁵Department of Cell Physiology, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan

Submitted 25 March 2009 ; accepted in final form 5 August 2009

The maxi-anion channel with a large single-channel conductance of >300 pS, and unknown molecular identity, is functionally expressed in a large variety of cell types. The channel is activated by a number of experimental maneuvers such as exposing cells to hypotonic or ischemic stress. The most effective and consistent method of activating it is patch membrane excision. However, the activation mechanism of the maxi-anion channel remains poorly understood at present. In the present study, involvement of phosphorylation/dephosphorylation in excision-induced activation was examined. In mouse mammary fibroblastic C127 cells, activity of the channel was suppressed by intracellular application of Mg-ATP, but not Mg-5'-adenylylimidodiphosphate (AMP-PNP), in a concentration-dependent manner. When a cocktail of broad-spectrum tyrosine phosphatase inhibitors was applied, channel activation was completely abolished, whereas inhibitors of serine/threonine protein phosphatases had no effect. On the other hand, protein tyrosine kinase inhibitors brought the channel out of an inactivated state. In mouse adult skin fibroblasts (MAFs) in primary culture, similar maxi-anion channels were found to be activated on membrane excision, in a manner sensitive to tyrosine phosphatase inhibitors. In MAFs isolated from animals deficient in receptor protein tyrosine phosphatase (RPTP), activation of the maxi-anion channel was significantly slower and less prominent compared with that observed in wild-type MAFs; however, channel activation was restored by transfection of the RPTP gene. Thus it is concluded that activation of the maxi-anion channel involves protein dephosphorylation mediated by protein tyrosine phosphatases that include RPTP in mouse fibroblasts, but not in C127 cells.

phosphorylation/dephosphorylation; protein tyrosine phosphatase; fibroblast