Reversible pore block of connexin channels by cyclodextrins.
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.
Locke
Darren
D
Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA. lockeda@umdnj.edu
Koreen
Irina V
IV
Liu
Jade Yu
JY
Harris
Andrew L
AL
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D000072259:Connexin 26; D017630:Connexins / Q000187:drug effects* / Q000378:metabolism; D003505:Cyclodextrins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D051381:Rats; D000097002:Gap Junction beta-1 Protein
D000072259:Connexin 26; D017630:Connexins; D003505:Cyclodextrins; D007473:Ion Channels; D008081:Liposomes; D000097002:Gap Junction beta-1 Protein; C000607043:Gjb2 protein, mouse; C000607044:Gjb2 protein, rat