Abstract
The maxi-anion channel has been suggested to represent a major ATP-conductive pathway mediating swelling-induced ATP release from many cell types. At the previous meeting, we reported that the channel is kept in the closed state while tyrosine-phosphorylated, whereas the dephosphorylation favours channel opening. However, the available spectrum of blockers for protein tyrosine phosphatases did not allow precise identification of this particular type of phosphatase. In the present study, we tested a possible involvement of the cloned receptor tyrosine phosphatase, RPTPζ, in the channel activation mechanism using molecular biological approaches. The rate of excision-induced maxi-anion channel activation was significantly slower in mouse adult fibroblasts (MAFs) derived from RPTPζ-deficient mice compared to MAFs from wild-type (WT) mice. Transfection of RPTPζ, but not the dominant-negative mutant, into the MAFs from RPTPζ-KO mice restored the maxi-anion channel activation rate to the level comparable to that of the WT MAFs. These results strongly suggest that RPTPζ represents an important part of the activation mechanism of the maxi-anion channel. The time-dependent ATP release from swollen MAFs derived from RPTPζ-KO mice was significantly lower compared to that from WT, suggesting that RPTPζ is involved in the swelling-induced release of ATP possibly via maxi-anion channel activation. [J Physiol Sci. 2008;58 Suppl:S208]
