Hypoxia inhibits human recombinant large conductance, Ca2+-activated K+ (maxi-K) channels by a mechanism which is membrane delimited and Ca2+ sensitive

Lewis, Anthony, Peers, Chris, Ashford, Michael L. J. and Kemp, Paul J. ORCID: https://orcid.org/0000-0003-2773-973X 2002. Hypoxia inhibits human recombinant large conductance, Ca2+-activated K+ (maxi-K) channels by a mechanism which is membrane delimited and Ca2+ sensitive. The Journal of Physiology 540 (3) , pp. 771-780. 10.1113/jphysiol.2001.013888

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Abstract

Large conductance, Ca2+-activated K+ (maxi-K) channel activity was recorded in excised, inside-out patches from HEK 293 cells stably co-expressing the α- and β-subunits of human brain maxi-K channels. At +50 mV, and in the presence of 300 nm [superscript]Ca 2+/i, single channel activity was acutely and reversibly suppressed upon reducing PO2 from 150 to > 40 mmHg by over 30 %. The hypoxia-evoked reduction in current was due predominantly to suppression in NPo, although a minor component was attributable to reduced unitary conductance of 8–12 %. Hypoxia caused an approximate doubling of the time constant for activation but was without effect on deactivation. At lower levels of [superscript]Ca 2+/i (30 and 100 nm), hypoxic inhibition did not reach significance. In contrast, 300 nm and 1 μm [superscript]Ca 2+/i both sustained significant hypoxic suppression of activity over the entire activating voltage range. At these two [superscript]Ca 2+/i levels, hypoxia evoked a positive shift in the activating voltage (by ∼10 mV at 300 nm and ∼25 mV at 1 μm). At saturating [Ca2+]i (100 μm), hypoxic inhibition was absent. Distinguishing between hypoxia-evoked changes in voltage- and/or [superscript]Ca 2+/i-sensitivity was achieved by evoking maximal channel activity using high depolarising potentials (up to +200 mV) in the presence of 300 nm or 100 μm [superscript]Ca 2+/i or in its virtual absence (> 1 nm). Under these experimental conditions, hypoxia caused significant channel inhibition only in the presence of 300 nm [superscript]Ca 2+/i. Thus, since regulation was observed in excised patches, maxi-K channel inhibition by hypoxia does not require soluble intracellular components and, mechanistically, is voltage independent and [superscript]Ca 2+/i sensitive.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH301 Biology
ISSN:	00223751
Last Modified:	17 Oct 2022 08:48
URI:	https://orca.cardiff.ac.uk/id/eprint/1117

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