Abstract
The maxi-anion channels express in a large variety of cell types. Its main physiological function is considered as a pathway for the regulated release of ATP and glutamate. The mechanisms by which the maxi-anion channel is regulated remain poorly understood. In the present study, we analyzed regulation mechanisms of the maxi-anion channel in inside-out patches excised from mammary gland C127 cells exposed to artificially designed intracellular solutions. An increase in the free Mg2+ concentration led to a dramatic increase in the rate of channel activation with half-maximal activation at 3 mM. Mg-ATP added to the intracellular solution greatly suppressed the channel activation with half-maximal inhibition at 36 μM. A non-hydrolysable analogue of ATP, AMP-PNP, did not suppress the channel activation. Broad-spectrum tyrosine phosphatase inhibitors, such as vanadate, dephostatine, molybdate and brometetramisole, effectively suppressed the channel activation. Tyrosine kinase inhibitors, such as AG18 and genestein, but not a broad spectrum serine-threonine kinase inhibitor, H7, restored the channel activity from its inactivated state. Taken together, it is concluded that the maxi-anion channel is regulated by magnesium and ATP, and suggested that the tyrosine dephosphorylation and phosphorylation processes are involved in the channel activation and inactivation, respectively. [J Physiol Sci. 2007;57 Suppl:S125]
