Rapid onset and calcium independence of the gap junction uncoupling induced by heptanol in cultured heart cells.
The kinetics of the reversible interruption of gap junction communication by the aliphatic alcohol heptanol and the possible mediation of an increase of the cytosolic Ca2+ concentration have been investigated in pairs of myocytes dissociated from neonatal rat ventricles and cultured for 2-3 days. Junctional communication was estimated by measuring either the cell-to-cell electrical conductance with a double whole-cell voltage-clamp method, or the rate constant of dye diffusion with the fluorescence recovery after photo-bleaching (gap FRAP) technique. Electrical coupling was seen to be abruptly interrupted (in less than 0.5 s) by heptanol (1-3 mM). The cytosolic Ca2+ concentration was not affected, even at a saturating heptanol concentration. Heptanol removal allowed a gradual re-opening of gap junctional channels, as shown by the recovery curve of the cell-to-cell conductance, which is 90% complete within 90 s. These data are consistent with a direct interaction of heptanol with channel proteins or with their lipid environment.
Bastide
B
B
Laboratoire de Physiologie Cellulaire, Unité de Recherche Associée au CNRS no. 1869, Poitiers, France.
Hervé
J C
JC
Cronier
L
L
Délèze
J
J
D015761:4-Aminopyridine / Q000494:pharmacology; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004594:Electrophysiology; D017629:Gap Junctions / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D019850:Heptanol; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats
D000438:Alcohols; D019850:Heptanol; D015761:4-Aminopyridine; D002118:Calcium