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Hypoxia activates ATP‐dependent potassium channels in inspiratory neurones of neonatal mice
Author(s) -
Mironov S. L.,
Langohr K.,
Haller M.,
Richter D. W.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.755bm.x
Subject(s) - biophysics , potassium channel , diazoxide , glibenclamide , chemistry , hyperpolarization (physics) , membrane potential , extracellular , gating , hypoxia (environmental) , conductance , tolbutamide , potassium , patch clamp , electrophysiology , atp sensitive potassium channel , medicine , endocrinology , biochemistry , oxygen , biology , stereochemistry , receptor , mathematics , organic chemistry , combinatorics , nuclear magnetic resonance spectroscopy , insulin , diabetes mellitus
1 The respiratory centre of neonatal mice (4 to 12 days old) was isolated in 700 μm thick brainstem slices. Whole‐cell K + currents and single ATP‐dependent potassium (K ATP ) channels were analysed in inspiratory neurones. 2 In cell‐attached patches, K ATP channels had a conductance of 75 pS and showed inward rectification. Their gating was voltage dependent and channel activity decreased with membrane hyperpolarization. Using Ca 2+ ‐containing pipette solutions the measured conductance was lower (50 pS at 1.5 mM Ca 2+ ), indicating tonic inhibition by extracellular Ca 2+ . 3 K ATP channel activity was reversibly potentiated during hypoxia. Maximal effects were attained 3‐4 min after oxygen removal from the bath. Hypoxic potentiation of open probability was due to an increase in channel open times and a decrease in channel closed times. 4 In inside‐out patches and symmetrical K + concentrations, channel currents reversed at about 0 mV. Channel activity was blocked by ATP (300‐600 μM), glibenclamide (10‐70 μM) and tolbutamide (100‐300 μM). 5 In the presence of diazoxide (10‐60 μM), the activity of K ATP channels was increased both in inside‐out, outside‐out and cell‐attached patches. In outside‐out patches, that remained within the slice after excision, the activity of K ATP channels was enhanced by hypoxia, an effect that could be mediated by a release of endogenous neuromodulators. 6 The whole‐cell K + current ( I K ) was inactivated at negative membrane potentials, which resembled the voltage dependence of K ATP channel gating. After 3‐4 min of hypoxia, K + currents at both hyperpolarizing and depolarizing membrane potentials increased. I K was partially blocked by tolbutamide (100‐300 μM) and in its presence, hypoxic potentiation of I K was abolished. 7 We conclude that K ATP channels are involved in the hypoxic depression of medullary respiratory activity.