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O2 sensing by recombinant TWIK-related halothane-inhibitable K+ channel-1 background K+ channels heterologously expressed in human embryonic kidney cells

O2 sensing by recombinant TWIK-related halothane-inhibitable K+ channel-1 background K+ channels heterologously expressed in human embryonic kidney cells
O2 sensing by recombinant TWIK-related halothane-inhibitable K+ channel-1 background K+ channels heterologously expressed in human embryonic kidney cells
Hypoxic inhibition of K+ channels provides a link between low O2 and cell function, and in glossopharyngeal neurons hypoxic inhibition of a TWIK-related halothane-inhibitable K+ channel-1 (THIK-1)-like background K+ channel regulates neuronal function. In the present study, we examined directly the O2 sensitivity of recombinant THIK-1 channels, expressed in human embryonic kidney (HE293) cells. THIK-1 expression conferred a moderately outwardly rectifying halothane-inhibited and arachidonic acid-potentiated K+ current and invoked a strongly hyperpolarized resting membrane potential. Endogenous K+ currents in untransfected cells were unaffected by either agent. Hypoxia (P(O2), 20 mmHg) reversibly inhibited THIK-1 currents and caused membrane depolarization, effects that were occluded by halothane. Neither the mitochondrial complex I inhibitors rotenone, myxothiazol and sodium cyanide, nor the NADPH oxidase inhibitors diphenylene iodonium and phenylarsine oxide, were effective in inhibiting the O2-sensitivity of THIK-1. Thus, hypoxic inhibition of THIK-1 occurs by a mechanism dissimilar to that which regulates the activity of other members of the background K+ channel family. Given the O2 sensitivity of THIK-1 channels and their abundant expression in the CNS, we raise for the first time the possibility of a physiological and/or pathological role for these channels during brain ischemia.
potassium channels, research support, family, human, inhibition, metabolism, membrane potentials, physiopathology, patch-clamp techniques, kidney, expression, potassium, neurons, brain, research, proteins, humans, transfection, oxygen, hypoxia-ischemia, role, biology, protein, activity, sodium, tandem pore domain, cell line, time, halothane, physiology, recombinant proteins
0306-4522
1087-1094
Campanucci, V.A.
6aa0a3a3-94ca-4eb2-aaf4-7156a90fea14
Brown, S.T.
419fa01c-b0ee-4673-949b-46fc5692ee55
Hudasek, K.
e03676ed-39f3-4a9d-8247-7b5fda380ea0
O'Kelly, I.M.
e640f28a-42f0-48a6-9ce2-cb5a85d08c66
Nurse, C.A.
1ac1e628-3e04-4f85-b26d-740709420262
Fearon, I.M.
4ef3ec41-ec62-4e73-beb6-c8548d5cdd5e
Campanucci, V.A.
6aa0a3a3-94ca-4eb2-aaf4-7156a90fea14
Brown, S.T.
419fa01c-b0ee-4673-949b-46fc5692ee55
Hudasek, K.
e03676ed-39f3-4a9d-8247-7b5fda380ea0
O'Kelly, I.M.
e640f28a-42f0-48a6-9ce2-cb5a85d08c66
Nurse, C.A.
1ac1e628-3e04-4f85-b26d-740709420262
Fearon, I.M.
4ef3ec41-ec62-4e73-beb6-c8548d5cdd5e

Campanucci, V.A., Brown, S.T., Hudasek, K., O'Kelly, I.M., Nurse, C.A. and Fearon, I.M. (2005) O2 sensing by recombinant TWIK-related halothane-inhibitable K+ channel-1 background K+ channels heterologously expressed in human embryonic kidney cells. Neuroscience, 135 (4), 1087-1094. (doi:10.1016/j.neuroscience.2005.07.009).

Record type: Article

Abstract

Hypoxic inhibition of K+ channels provides a link between low O2 and cell function, and in glossopharyngeal neurons hypoxic inhibition of a TWIK-related halothane-inhibitable K+ channel-1 (THIK-1)-like background K+ channel regulates neuronal function. In the present study, we examined directly the O2 sensitivity of recombinant THIK-1 channels, expressed in human embryonic kidney (HE293) cells. THIK-1 expression conferred a moderately outwardly rectifying halothane-inhibited and arachidonic acid-potentiated K+ current and invoked a strongly hyperpolarized resting membrane potential. Endogenous K+ currents in untransfected cells were unaffected by either agent. Hypoxia (P(O2), 20 mmHg) reversibly inhibited THIK-1 currents and caused membrane depolarization, effects that were occluded by halothane. Neither the mitochondrial complex I inhibitors rotenone, myxothiazol and sodium cyanide, nor the NADPH oxidase inhibitors diphenylene iodonium and phenylarsine oxide, were effective in inhibiting the O2-sensitivity of THIK-1. Thus, hypoxic inhibition of THIK-1 occurs by a mechanism dissimilar to that which regulates the activity of other members of the background K+ channel family. Given the O2 sensitivity of THIK-1 channels and their abundant expression in the CNS, we raise for the first time the possibility of a physiological and/or pathological role for these channels during brain ischemia.

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More information

Published date: 2005
Keywords: potassium channels, research support, family, human, inhibition, metabolism, membrane potentials, physiopathology, patch-clamp techniques, kidney, expression, potassium, neurons, brain, research, proteins, humans, transfection, oxygen, hypoxia-ischemia, role, biology, protein, activity, sodium, tandem pore domain, cell line, time, halothane, physiology, recombinant proteins

Identifiers

Local EPrints ID: 59551
URI: http://eprints.soton.ac.uk/id/eprint/59551
ISSN: 0306-4522
PURE UUID: c401e026-dfbf-429d-b88d-13e162694bd6

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Date deposited: 03 Sep 2008
Last modified: 13 Mar 2019 20:30

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Contributors

Author: V.A. Campanucci
Author: S.T. Brown
Author: K. Hudasek
Author: I.M. O'Kelly
Author: C.A. Nurse
Author: I.M. Fearon

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