Potential identification of the O2-sensitive K+ current in a human neuroepithelial body-derived cell line

Am J Physiol. 1999 Jan;276(1):L96-L104. doi: 10.1152/ajplung.1999.276.1.L96.

Abstract

Whole cell recording of H-146 cells revealed that the outward K+ current was completely inhibited by quinidine (IC50 approximately 17 microM). In contrast, maximal concentrations of 4-aminopyridine (4-AP; >/=10 mM) reversibly blocked only approximately 60% (IC50 approximately 1.52 mM). Ten millimolar 4-AP had no effect on the inhibition by hypoxia, which reduced current density from approximately 27 to approximately 13 pA/pF, whereas 1 mM quinidine abolished the hypoxic effect. In current clamp, 10 mM 4-AP depolarized the cell by approximately 18 mV and hypoxia caused further reversible depolarization of approximately 4 mV. One millimolar quinidine collapsed the membrane potential and abrogated any further hypoxic depolarization. RT-PCR revealed expression of the acid-sensitive, twin P domain K+ channel TASK but not of TWIK, TREK, or the known hypoxia-sensitive Kv2.1, which was confirmed by sequencing and further PCR with primers to the coding region of TASK. However, a reduction in extracellular pH had no effect on K+ current. Thus, although the current more closely resembles TWIK than TASK pharmacologically, structurally the reverse appears to be true. This suggests that a novel acid-insensitive channel related to TASK may be responsible for the hypoxia-sensitive K+ current of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence / genetics
  • Carcinoma, Small Cell / physiopathology
  • Chemoreceptor Cells / physiology*
  • Electric Conductivity
  • Epithelium / innervation
  • Humans
  • Hydrogen-Ion Concentration
  • Hypoxia / physiopathology
  • Lung / innervation*
  • Lung Neoplasms / physiopathology
  • Membrane Potentials / physiology
  • Molecular Sequence Data
  • Oxygen / metabolism*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Potassium Channels
  • Oxygen