Long-chain n-alkanols and arachidonic acid interfere with the V(m)-sensitive gating mechanism of gap junction channels

Robert Weingart, Feliksas F. Bukauskas

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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, g(j), 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 g(j). Hyperpolarization of both cells led to a recovery of g(j). Systematic studies revealed that this phenomenon is caused by a shift of the sigmoidal relationship g(j(ss)) = f(V(m)) towards more negative values of V(m)(where g(j(ss)) = conductance at steady-state; V(m) = 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 g(j(ss)) = f(V(m)), arachidonic channel records gained from induced cell pairs revealed that the lipophilic agents interfere with the V(m)-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 V(m) or washout of the lipophilic agents gave rise to the inverse sequence of events. The single-channel conductances γ(j(main state)) and γ(j(residual state)) were not affected by n-heptanol. We conclude that long-chain n-alkanols and arachidonic acid interact with the V(m)-sensitive gating mechanism.

Original languageEnglish (US)
Pages (from-to)310-319
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Volume435
Issue number2
DOIs
StatePublished - Feb 18 1998

Keywords

  • Arachidonic acid
  • Chemical uncoupling
  • Insect gap junctions
  • Lipophilic agents
  • N-Alkanols
  • Slow current transitions
  • V(m)-sensitive gating

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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