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

I. O'Kelly, R. H. Stephens, C. Peers, P. J. Kemp

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Whole cell recording of H-146 cells revealed that the outward K+ current was completely inhibited by quinidine (IC50 ~17 μM). In contrast, maximal concentrations of 4-aminopyridine (4-AP; ≥ 10 mM) reversibly blocked only ~60% (IC50 ~1.52 mM). Ten millimolar 4-AP had no effect on the inhibition by hypoxia, which reduced current density from ~27 to ~13 pA/pF, whereas 1 mM quinidine abolished the hypoxic effect. In current clamp, 10 mM 4-AP depolarized the cell by ~18 mV and hypoxia caused further reversible depolarization of ~4 mV. One millimolar quinidine collapsed the membrane potential and abrogated any further hypoxic depolarization. RTPCR 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.
    Original languageEnglish
    Pages (from-to)L96-L104
    JournalAJP: Lung Cellular and Molecular Physiology
    Volume276
    Issue number1
    Publication statusPublished - Jan 1999

    Keywords

    • Chemoreceptor
    • Hypoxia
    • Potassium channels
    • TASK

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