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J. Biol. Chem., Vol. 279, Issue 22, 22883-22892, May 28, 2004

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Reversible Pore Block of Connexin Channels by Cyclodextrins^*

Darren Locke, Irina V. Koreen, Jade Yu Liu, and Andrew L. Harris

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

Cyclodextrins (CDs), a series of hollow cyclic glucosaccharides, can reversibly block molecular permeation through channels formed by connexin-32 and/or connexin-26 reconstituted into liposomes. The character of the block changes as a function of the size of the CD relative to the connexin pore diameter, suggesting that the block occurs via entry of the CD into the pore lumen and occlusion of the permeability pathway. The block occurs only when the CD is applied to the side of the pore that is normally cytoplasmic and not from the side that is normally extracellular. The block is potentiated when organic analytes are sequestered in the hydrophobic interior of the CDs. CDs may be useful as molecular tools with which to explore the structure of the connexin pore and to alter molecular movement through connexin channels.

Received for publication, February 23, 2004 , and in revised form, March 23, 2004.

^* 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.

To whom correspondence should be addressed: Dept. of Pharmacology and Physiology, Medical Sciences Bldg. I-643, New Jersey Medical School, UMDNJ, 185 South Orange Ave., Newark, NJ 07103. Tel.: 973-972-1619; Fax: 973-972-4554; E-mail: lockeda{at}umdnj.edu.

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