Hypoxia activates ATP-dependent potassium channels in inspiratory neurones of neonatal mice.
1. The respiratory centre of neonatal mice (4 to 12 days old) was isolated in 700 micro(m) thick brainstem slices. Whole-cell K+ currents and single ATP-dependent potassium (KATP) channels were analysed in inspiratory neurones. 2. In cell-attached patches, KATP channels had a conductance of 75 pS and showed inward rectification. Their gating was voltage dependent and channel activity decreased with membrane hyperpolarization. Using Ca2+-containing pipette solutions the measured conductance was lower (50 pS at 1.5 mM Ca2+), indicating tonic inhibition by extracellular Ca2+. 3. KATP 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 microM), glibenclamide (10-70 microM) and tolbutamide (100-300 microM). 5. In the presence of diazoxide (10-60 microM), the activity of KATP 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 KATP channels was enhanced by hypoxia, an effect that could be mediated by a release of endogenous neuromodulators. 6. The whole-cell K+ current (IK) was inactivated at negative membrane potentials, which resembled the voltage dependence of KATP channel gating. After 3-4 min of hypoxia, K+ currents at both hyperpolarizing and depolarizing membrane potentials increased. IK was partially blocked by tolbutamide (100-300 microM) and in its presence, hypoxic potentiation of IK was abolished. 7. We conclude that KATP channels are involved in the hypoxic depression of medullary respiratory activity.
Mironov
S L
SL
II Department of Physiology, University of Gottingen, Humboldtallee 23, Gottingen 37073, Germany.
Langohr
K
K
Haller
M
M
Richter
D W
DW
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects; D008526:Medulla Oblongata / Q000098:blood supply / Q000737:chemistry / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D012119:Respiration / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D003981:Diazoxide; D005905:Glyburide; D002118:Calcium