Kinetic interaction of fatty acids with outwardly rectifying chloride channels

Tzyh Chang Hwang, Marie E. Egan, William B. Guggino

Research output: Contribution to journalArticlepeer-review

Abstract

Outwardly rectifying Cl channels are present in many tissues and are thought to be defective in Cl-secreting epithelia involved in cystic fibrosis (CF). Polyunsaturated fatty acids in the cis, but not the trans configuration cause rapid intrruptions in the outwardly rectifying Cl channel currents. In this report, the effects of other physiologically relevant fatty acids were tested. The voltage dependence and the effects of variations in pipette Cl on the kinetics of the interaction of fatty acids with the channel were explored. Leukotrienes C4 and D4 cause rapid interruptions in the single-channel currents with the same potcncy as arachidonic acid and other polyunsaturated fatty acids. The off-rate constant, Koff, evaluated in excised patches in the presence of 30 μM arachidonic acid is voltage dependent at positive voltages, varying ɛ-fold per 68 mV, but voltage independent at negative voltages. In contrast, the on-rate constant, Kon, is voltage independent both at positive and negative voltages. Variations in pipette Cl between 150 and 300 mV do not affect the voltage dependence of Koff. Similarly, changing pipette [Cl] between 80 and 300 mM does not affect either Koff or Kon. These data suggest that fatty acids do not act as simple, charged, open-channel blockers.

Original languageEnglish (US)
Pages (from-to)308-315
Number of pages8
JournalCellular Physiology and Biochemistry
Volume2
Issue number6
DOIs
StatePublished - 1992

Keywords

  • Arachidonic acid
  • Cystic fibrosis
  • Leukotrienes
  • Patch clamping
  • Single-channel kinetics

ASJC Scopus subject areas

  • Physiology

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