Experimental diabetes alters connexin43 derived gap junction permeability in short-term cultures of rat corporeal vascular smooth muscle cells.
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.
Brink
Peter R
PR
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
Valiunas
Virginijus
V
Wang
Hong-Zhan
HZ
Zhao
Weixin
W
Davies
Kelvin
K
Christ
George J
GJ
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
D018031:Connexin 43