Long-chain n-alkanols and arachidonic acid interfere with the Vm-sensitive gating mechanism of gap junction channels.
Experiments were carried out on preformed cell pairs and induced cell pairs of an insect cell line (mosquito Aedes albopictus, clone C6/36). The coupling conductance, gj, was determined with the dual voltage-clamp method. Exposure of preformed cell pairs to lipophilic agents, such as long-chain n-alkanols (n-hexanol, n-heptanol, n-octanol, n-nonanol, n-decanol) or arachidonic acid, provoked a decrease in gj. Hyperpolarization of both cells led to a recovery of gj. Systematic studies revealed that this phenomenon is caused by a shift of the sigmoidal relationship gj(ss) = f(Vm) towards more negative values of Vm (where gj(ss) = conductance at steady-state; Vm = membrane potential). The shift was dose dependent, it developed with time and was reversible. The longer the hydrocarbon chain of n-alkanols, the lower was the concentration required to produce a given shift. Besides shifting the function gj(ss) = f(Vm), arachidonic acid decreased the maximal conductance, gj(max). Single-channel records gained from induced cell pairs revealed that the lipophilic agents interfere with the Vm-sensitive slow channel gating mechanism. Application provoked slow current transitions (transition time: 5-40 ms) between an open state of the channel (i.e. main state or residual state) and the closed state; subsequently, fast channel transitions (transition time: < 2 ms) involving the main state and the residual state ceased completely. Hyperpolarization of Vm or washout of the lipophilic agents gave rise to the inverse sequence of events. The single-channel conductances gammaj(main state) and gammaj(residual state) were not affected by n-heptanol. We conclude that long-chain n-alkanols and arachidonic acid interact with the Vm-sensitive gating mechanism.
Weingart
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Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland.
Bukauskas
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D020003:1-Octanol / Q000494:pharmacology; D000330:Aedes; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002460:Cell Line; D004553:Electric Conductivity; D005233:Fatty Alcohols / Q000494:pharmacology; D017629:Gap Junctions / Q000502:physiology*; D019850:Heptanol / Q000494:pharmacology; D000441:Hexanols / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials
D000438:Alcohols; D005233:Fatty Alcohols; D000441:Hexanols; D007473:Ion Channels; D016718:Arachidonic Acid; C036260:1-hexanol; C029383:n-decyl alcohol; D019850:Heptanol; D020003:1-Octanol