ATP signaling is deficient in cultured pannexin1-null mouse astrocytes
Article first published online: 12 APR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 60, Issue 7, pages 1106–1116, July 2012
How to Cite
Suadicani, S. O., Iglesias, R., Wang, J., Dahl, G., Spray, D. C. and Scemes, E. (2012), ATP signaling is deficient in cultured pannexin1-null mouse astrocytes. Glia, 60: 1106–1116. doi: 10.1002/glia.22338
- Issue published online: 8 MAY 2012
- Article first published online: 12 APR 2012
- Manuscript Accepted: 16 MAR 2012
- Manuscript Received: 17 NOV 2011
- National Institutes of Health National Institute of Neurological Disorders and Stroke. Grant Numbers: NS052245, NS041282
- American Heart Association. Grant Number: 0735377N
- gap junction;
- P2X receptor;
- calcium waves;
Pannexins (Panx1, 2, and 3) comprise a group of proteins expressed in vertebrates that share weak yet significant sequence homology with the invertebrate gap junction proteins, the innexins. In contrast to the other vertebrate gap junction protein family (connexin), pannexins do not form intercellular channels, but at least Panx1 forms nonjunctional plasma membrane channels. Panx1 is ubiquitously expressed and has been shown to form large conductance (500 pS) channels that are voltage dependent, mechanosensitive, and permeable to relatively large molecules such as ATP. Pharmacological and knockdown approaches have indicated that Panx1 is the molecular substrate for the so-called “hemichannel” originally attributed to connexin43 and that Panx1 is the pore-forming unit of the P2X7 receptor. Here, we describe, for the first time, conductance and permeability properties of Panx1-null astrocytes. The electrophysiological and fluorescence imaging analyses performed on these cells fully support our previous pharmacological and Panx1 knockdown studies that showed profoundly lower dye uptake and ATP release than wild-type untreated astrocytes. As a consequence of decreased ATP paracrine signaling, intercellular calcium wave spread is altered in Panx1-null astrocytes. Moreover, we found that in astrocytes as in Panx1-expressing oocytes, elevated extracellular K+ activates Panx1 channels independently ofmembrane potential. Thus, on the basis of our present findings and our previous report, we propose that Panx1 channels serve as K+ sensors for changes in the extracellular milieu such as those occurring under pathological conditions. © 2012 Wiley Periodicals, Inc.