HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 24, 16727-16739, June 16, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/24/16727    most recent M600136200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ayad, W. A. Articles by Harris, A. L. Search for Related Content PubMed PubMed Citation Articles by Ayad, W. A. Articles by Harris, A. L. Social Bookmarking                      What's this?

Heteromeric, but Not Homomeric, Connexin Channels Are Selectively Permeable to Inositol Phosphates^*

From the Department of Pharmacology and Physiology, New Jersey Medical School, Newark, New Jersey 07103

Previous work has shown that channels formed by both connexin (Cx)26 and Cx32 (heteromeric Cx26/Cx32 hemichannels) are selectively permeable to cAMP and cGMP. To further investigate differential connexin channel permeability among second messengers, and the influence of connexin channel composition on the selectivity, the permeability of inositol phosphates with one to four phosphate groups through homomeric Cx26, homomeric Cx32, and heteromeric Cx26/Cx32 channels was examined. Connexin channels were purified from transfected HeLa cells and from rat, mouse, and guinea pig livers, resulting in channels with a broad range of Cx26/Cx32 aggregate ratios. Permeability to inositol phosphates was assessed by flux through reconstituted channels. Surprisingly, myoinositol and all inositol phosphates tested were permeable through homomeric Cx32 and homomeric Cx26 channels. Even more surprising, heteromeric Cx26/Cx32 channels showed striking differences in permeability among inositol phosphates with three or four phosphate groups and among isomers of inositol triphosphate. Thus, heteromeric channels are selectively permeable among inositol phosphates, whereas the corresponding homomeric channels are not. There was no discernible difference in the permeability of channels with similar Cx26/Cx32 ratios purified from native and heterologous sources. The molecular selectivity of heteromeric channels among three inositol triphosphates could not be accounted for by simple connexin isoform stoichiometry distributions and therefore may depend on specific isoform radial arrangements within the hexameric channels. Dynamic regulation of channel composition in vivo may effectively and efficiently modulate intercellular signaling by inositol phosphates.

Received for publication, January 5, 2006 , and in revised form, March 17, 2006.

^* This work was supported by National Institutes of Health Grants GM36044 and GM61406 (to A. L. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 973-972-5021; Fax: 973-972-4554; E-mail: elsayewa{at}umdnj.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. A. Goodenough and D. L. Paul Gap Junctions Cold Spring Harb Perspect Biol, July 1, 2009; 1(1): a002576 - a002576. [Abstract] [Full Text] [PDF]

				J. K. VanSlyke, C. C. Naus, and L. S. Musil Conformational Maturation and Post-ER Multisubunit Assembly of Gap Junction Proteins Mol. Biol. Cell, May 1, 2009; 20(9): 2451 - 2463. [Abstract] [Full Text] [PDF]

				F. Anselmi, V. H. Hernandez, G. Crispino, A. Seydel, S. Ortolano, S. D. Roper, N. Kessaris, W. Richardson, G. Rickheit, M. A. Filippov, et al. ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear PNAS, December 2, 2008; 105(48): 18770 - 18775. [Abstract] [Full Text] [PDF]

				B. E. Isakson Localized expression of an Ins(1,4,5)P3 receptor at the myoendothelial junction selectively regulates heterocellular Ca2+ communication J. Cell Sci., November 1, 2008; 121(21): 3664 - 3673. [Abstract] [Full Text] [PDF]

				M. Lahne and J. E. Gale Damage-Induced Activation of ERK1/2 in Cochlear Supporting Cells Is a Hair Cell Death-Promoting Signal That Depends on Extracellular ATP and Calcium J. Neurosci., May 7, 2008; 28(19): 4918 - 4928. [Abstract] [Full Text] [PDF]

				A. L. Harris Connexin Specificity of Second Messenger Permeation: Real Numbers At Last J. Gen. Physiol., March 31, 2008; 131(4): 287 - 292. [Full Text] [PDF]