Physiological mechanisms for the modulation of pannexin 1 channel activity.
It is widely recognized that ATP, along with other nucleotides, subserves important intercellular signalling processes. Among various nucleotide release mechanisms, the relatively recently identified pannexin 1 (Panx1) channel is gaining prominence by virtue of its ability to support nucleotide permeation and release in a variety of different tissues. Here, we review recent advances in our understanding of the factors that control Panx1 channel activity. By using electrophysiological and biochemical approaches, diverse mechanisms that dynamically regulate Panx1 channel function have been identified in various settings; these include, among others, activation by caspase-mediated channel cleavage in apoptotic immune cells, by G protein-coupled receptors in vascular smooth muscle, by low oxygen tension in erythrocytes and neurons, by high extracellular K(+) in various cell types and by stretch/strain in airway epithelia. Delineating the distinct mechanisms of Panx1 modulation that prevail in different physiological contexts provides the possibility that these channels, and ATP release, could ultimately be targeted in a context-dependent manner.
Department of Pharmacology, University of Virginia, Charlottesville, VA, USA. jks6f@virginia.edu
Joanna K
JK
Sandilos
Douglas A
DA
Bayliss
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017630:Connexins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D040542:Mechanotransduction, Cellular; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010539:Permeability; D021381:Protein Transport; D011983:Receptors, Purinergic / Q000378:metabolism
D017630:Connexins; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D010447:Peptide Hydrolases