TY - JOUR
T1 - Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communications
AU - Zhao, Hong Bo
PY - 2005/4
Y1 - 2005/4
N2 - A gap junction is composed of two hemichannels and possesses a relatively large pore size (∼ 10-15 Å), 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.
AB - A gap junction is composed of two hemichannels and possesses a relatively large pore size (∼ 10-15 Å), 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.
KW - Deafness
KW - Gap junction
KW - Hemichannel
KW - Inner ear
KW - Metabolism
KW - Selectivity
UR - http://www.scopus.com/inward/record.url?scp=18844362687&partnerID=8YFLogxK
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U2 - 10.1111/j.1460-9568.2005.04031.x
DO - 10.1111/j.1460-9568.2005.04031.x
M3 - Article
C2 - 15869481
AN - SCOPUS:18844362687
SN - 0953-816X
VL - 21
SP - 1859
EP - 1868
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 7
ER -