Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communications.
Abstract A gap junction is composed of two hemichannels and possesses a relatively large pore size ( approximately 10-15 A), allowing passage of ions and molecules up to 1 kDa. Here, we report that connexin hemichannels and gap junctions in the guinea pig cochlea had significant charge selectivity among permeating molecules. In coincubation with anionic and cationic fluorescent dyes, hemichannel permeability in isolated cochlear supporting cells showed significant charge selectivity; 31% of cells had only cationic dye influx and 6% of cells had only anionic dye influx. Charge-selective influx contrary to dye size was also found, indicating charge as a dominant determinant in permeability. The cell-cell gap junctional permeability was consistent with hemichannel permeability and also showed strong charge selectivity; the permeation of anionic dyes was slower than that of cationic probes in the cochlear sensory epithelium. With a combination of immunofluorescent staining for connexin26 (Cx26) and Cx30, which are the predominant connexin isoforms in the cochlea, Cx26 was demonstrated to correlate with anionic permeability. The data indicated that cochlear gap junctions have strong charge selectivity in molecular permeability and metabolic communication. Cx26 mutation may induce specific, irreparable impairment in intercellular signalling and energy and nutrient supplies in the cochlea, causing cell degeneration and hearing loss, given that many important cell-signalling and nutrient and energy molecules (e.g. IP3, ATP, cAMP and cGMP) are anions.
Zhao
Hong-Bo
HB
Department of Surgery--Otolaryngology, University of Kentucky Medical Center, Lexington, Kentucky, 40536, USA. hzhao2@uky.edu
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002452:Cell Count; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology* / Q000187:drug effects; D000072259:Connexin 26; D017630:Connexins / Q000145:classification / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence / Q000379:methods; D013997:Time Factors
D000345:Affinity Labels; D000838:Anions; D000893:Anti-Inflammatory Agents; D002412:Cations; D017630:Connexins; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010975:Platelet Aggregation Inhibitors; D000072259:Connexin 26; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C017199:2',3'-dialdehyde ATP; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D011335:Proadifen; D006034:Glycyrrhetinic Acid; D002118:Calcium