QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jpet.108.146365v1 328/2/409    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ma, W. Articles by Surprenant, A. Search for Related Content PubMed PubMed Citation Articles by Ma, W. Articles by Surprenant, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

CELLULAR AND MOLECULAR

Pharmacological Characterization of Pannexin-1 Currents Expressed in Mammalian Cells

Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom

Pannexin (Panx) 1 is a widely expressed protein that shares structural, but not amino acid, homology with gap junction proteins, the connexins. Panx1 does not form gap junctions in mammalian cells, but it may function as a plasma membrane hemichannel. Little is known of the pharmacological properties of panx1 expression in mammalian cells. Here, we identify three variants in the human PANX1 gene. We expressed these variants and mouse Panx1 in mammalian cells and compared Panx1-induced currents. All human Panx1 variants and the mouse Panx1 showed identical protein expression levels, localization patterns, and functional properties, although the frequency of functional expression was species-dependent. Panx1 currents were independent of changes in extracellular or intracellular calcium or phospholipase C transduction. We found compounds that inhibited Panx1 currents with a rank order of potency: carbenoxolone > disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) disodium 4-acetamido-4'-isothiocyanato-stilben-2,2'-disulfonate 5-nitro-2-(3-phenylpropylamino)benzoic acid > indanyloxyacetic acid 94 >> probenecid >> flufenamic acid = niflumic acid. Triphosphate nucleotides (ATP, GTP, and UTP) rapidly and reversibly inhibited Panx1 currents via mechanism(s) independent of purine receptors. When Panx1 was coexpressed with purinergic P2X₇ receptor (P2X₇R), DIDS was found to act as a P2X₇R antagonist to inhibit ATP-evoked currents, but none of the other compounds inhibited P2X₇R currents. This is the first detailed pharmacological characterization of Panx1-mediated currents in mammalian cells and sheds new, although contradictory, light on the hypothesis that Panx1 acts as a hemichannel to allow passage of large molecules in response to P2X₇R activation.

Address correspondence to: Annmarie Surprenant, Faculty of Life Sciences, Michael Smith Building D3315, University of Manchester, Manchester M13 9PT, United Kingdom. E-mail: a.surprenant{at}manchester.ac.uk

This article has been cited by other articles:

				M. Lamkanfi, J. L. Mueller, A. C. Vitari, S. Misaghi, A. Fedorova, K. Deshayes, W. P. Lee, H. M. Hoffman, and V. M. Dixit Glyburide inhibits the Cryopyrin/Nalp3 inflammasome J. Cell Biol., October 5, 2009; 187(1): 61 - 70. [Abstract] [Full Text] [PDF]