Reversible inhibition of gap junctional communication elicited by several classes of lipophilic compounds in cultured rat cardiomyocytes.
BACKGROUND
Electrical coupling between cardiac muscle cells is mediated by specialized sites of plasma membrane termed 'gap junctions', which consist of clusters of transmembrane channels that directly link the cytoplasmic compartments of neighbouring cells and allow direct transfer of small ions and molecules. These structures provide low resistance electrical pathways between cardiac cells, necessary for rapid impulse propagation and, thus, coordinate contraction of the myocardium.


OBJECTIVE
To investigate the effects of derivatives of sex steroid hormones and of some of their antagonists on junctional communication in pairs of cultured ventricular myocytes of neonatal rats.


RESULTS
Short term (15 min) exposures to some of these lipophilic compounds led, in a concentration range 1 to 22 microM, to a reversible inhibition of cell to cell communication. None of these uncoupling treatments altered the cytosolic calcium concentration, examined by means of a fluorescence indicator. The uncoupling effect of sex hormones persisted in the presence of blockers of their respective nuclear receptors (eg, cyproterone acetate for testosterone and tamoxifen for 17-beta-estradiol). Some of these blockers (tamoxifen, clomiphene) were able to impair gap junctional communication, whereas others (nafoxidine and cyproterone acetate) had no effect. None of protein kinase C, cAMP-dependent protein kinase and protein tyrosine kinase pathways seemed to be involved in these effects.


CONCLUSIONS
Several lipophilic compounds able to hinder cell to cell communication have also been seen to affect voltage-activated or ligand-activated ionic channels. Lipophilic molecules with an appropriate molecular skeleton could insert into the membrane, with resulting destabilization and unspecific closure of membrane channels.
Verrecchia
F
F
Laboratoire de Physiologie Cellulaire, Centre National de la Recherche Scientifique No 1869, Poitieres, France.
Hervé
J C
JC
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D046508:Culture Techniques; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D013256:Steroids / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D013256:Steroids; D013629:Tamoxifen; D013739:Testosterone; D004958:Estradiol