Nucleotide receptors activate cation, potassium, and chloride currents in a liver cell line

J. G. Fitz, A. H. Sostman

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50 Scopus citations

Abstract

By use of whole cell patch-clamp techniques, the effects of extracellular ATP on membrane ion currents of HTC cells from a rat liver tumor line were evaluated. ATP (500 μM) or the nonhydrolyzable analogue adenosine 5'-O-(3- thiotriphosphate) caused sequential activation of three currents: I(cat) (- 1,325 ± 255 pA at -80 mV) occurred early, was due to increased Na+ and K+ permeability, was present in 56% of 64 consecutive cells, and rapidly inactivated; I(K) (274 ± 45 pA at 0 mV) was present in 59% of cells and also inactivated; and I(Cl) (1,172 ± 237 pA at +60 mV) was present in 94% of studies, was sustained, and exhibited outward rectification of the current- voltage relation. All three currents were present in 39% of cells. Increasing intracellular Ca2+ concentration ([Ca2+](i)) by exposure to the 5'- nucleotide receptor agonist UTP (500 μM) or to thapsigargin activated I(cat) and I(K) but not I(Cl), whereas increasing ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid in the pipette (≥ 5 mM) inhibited ATP- dependent activation of I(cat) and I(K) but not I(Cl). A P(2x)-preferring agonist α,β-methylene ATP (500 μM) did not activate currents; a P(2y)- preferring agonist 2-methylthioadenosine triphosphate activated I(cat) and I(K) at concentrations of 500 μM but not 50 μM. In perforated patch recordings, ATP produced triphasic changes in membrane potential with initial depolarization due to I(cat), subsequent hyperpolarization due to I(K), and a later sustained depolarization due to I(Cl). These findings indicate that ATP modulates HTC cell ion permeability through initial activation of I(cat) and I(K) mediated by 5'-nucleotide receptors which mobilize [Ca2+](i), and sustained activation of I(Cl) through a separate Ca2+-independent mechanism.

Original languageEnglish (US)
Pages (from-to)G544-G553
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume266
Issue number4 29-4
DOIs
StatePublished - Jan 1 1994

Keywords

  • ion channels
  • patch clamp
  • purinergic receptors

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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