title: Experimental diabetes alters connexin43 derived gap junction permeability in short-term cultures of rat corporeal vascular smooth muscle cells.
abstract: OBJECTIVE
  Intercellular communication through gap junctions was assessed in 8 to 10-week STZ diabetic rats to evaluate diabetes related effects on gap junctional conductance and permeability in short-term cultures of corporeal myocytes.
  
  
  METHODS
  Rats were made diabetic by a single intraperitoneal injection of STZ. Eight to 10 weeks later erectile function was evaluated in vivo and corporeal tissue was harvested to isolate corporeal myocytes. Dual whole cell patch clamp studies of intercellular communication through connexin43 (Cx43) derived gap junction channels were done in short-term, ie passages 0 to 2, cultured corporeal myocytes excised from STZ diabetic rats with documented erectile impairment as well as in myocytes from age matched control rats.
  
  
  RESULTS
  No differences in macroscopic junctional conductance, single channel conductance or open probability were detected between myocytes from age matched control and STZ diabetic rats, confirming the lack of diabetes related alterations in Cx43 gating or conductance. However, fluorescence dye transfer experiments revealed a marked 3-fold increase in Cx43 mediated junctional permeability in the absence of any detectable change in Cx43 protein expression.
  
  
  CONCLUSIONS
  These data suggest that an alteration in the selectivity filter of Cx43 in diabetic animals affects the permeability of specifically sized and charged solutes. To our knowledge these studies provide the first evidence of a diabetes related increase in intercellular permselectivity in corporeal myocytes and, thus, they may have important implications for diabetes related erectile dysfunction.
authors.affiliation: Department of Physiology and Biophysics and Institute for Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, USA. peter.brink@sunysb.edu
authors.forename: Peter R
authors.initials: PR
authors.lastname: Brink
authors.forename: Virginijus
authors.initials: V
authors.lastname: Valiunas
authors.forename: Hong-Zhan
authors.initials: HZ
authors.lastname: Wang
authors.forename: Weixin
authors.initials: W
authors.lastname: Zhao
authors.forename: Kelvin
authors.initials: K
authors.lastname: Davies
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D018031:Connexin 43 / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004594:Electrophysiology; D017629:Gap Junctions / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D010413:Penis / Q000098:blood supply*; D051381:Rats; D013997:Time Factors
chemical_list: D018031:Connexin 43