The maxi-anion channel: a classical channel playing novel roles through an unidentified molecular entity

The maxi-anion channel is widely expressed and found in almost every part of the body. The channel is activated in response to osmotic cell swelling, to excision of the membrane patch, and also to some other physiologically and pathophysiologically relevant stimuli, such as salt stress in kidney macula densa as well as ischemia/hypoxia in heart and brain. Biophysically, the maxi-anion channel is characterized by a large single-channel conductance of 300-400 pS, which saturates at 580-640 pS with increasing the Cl- concentration. The channel discriminates well between Na+ and Cl-, but is poorly selective to other halides exhibiting weak electric-field selectivity with an Eisenman's selectivity sequence I. The maxi-anion channel has a wide pore with an effective radius of similar to 1.3 nm and permits passage not only of Cl- but also of some intracellular large organic anions, thereby releasing major extracellular signals and gliotransmitters such as glutamate(-) and ATP(4-). The channel-mediated efflux of these signaling molecules is associated with kidney tubuloglomerular feedback, cardiac ischemia/hypoxia, as well as brain ischemia/hypoxia and excitotoxic neurodegeneration. Despite the ubiquitous expression, well-defined properties and physiological/pathophysiological significance of this classical channel, the molecular entity has not been identified. Molecular identification of the maxi-anion channel is an urgent task that would greatly promote investigation in the fields not only of anion channel but also of physiological/pathophysiological signaling in the brain, heart and kidney.