抄録
Electrogenic translocation of ATP via an anion channel is considered as one of mechanisms of the regulated ATP release. We have demonstrated that ATP-releasing stimuli, such as osmotic and salt stress, ischemia and hypoxia induce activation of maxi-anion channels in mammary C127 cells (Sabirov et al., J. Gen. Physiol. 2001, 118: 251-266), kidney macula densa (Bell et al., Proc. Natl. Acad. Sci. U S A 2003, 100: 4322-4327), cardiomyocytes (Dutta et al., J. Physiol. 2004, 559: 799-812) and brain astrocytes (Liu et al., Glia 2006, 54: 343-357). These channels were found to have a large unitary conductance (around 400 pS) and a weak ATP-binding site (with Kd of around 12 mM) in the middle of the pore. We observed tangible ATP-mediated currents and estimated the permeability ratio PATP/PCl of about 0.1. The channel pore size (around 1.3 nm; Sabirov & Okada, Biophys. J. 2004 87: 1672-1685) was considerably larger than the radii of ATP4− and MgATP2− (around 0.6 nm) suggesting that the nanoscopic maxi-anion channel pore provides a sufficient room to accommodate ATP. The channel and swelling-induced ATP release shared the same pharmacological profile, i.e., sensitivity to Gd3+, SITS and NPPB, but not to phloretin, niflumic acid or glibenclamide. Thus, we propose that maxi-anion channel fulfills a general physiological function of a regulated electrogenic conduit for ATP in purinergic cell-to-cell signaling. [J Physiol Sci. 2007;57 Suppl:S62]
