Hypoxia-induced functional alterations in adult rat neocortex.
1. Brief periods of hypoxia (2-7 min) were induced in rat neocortical slices maintained in an interface-type recording chamber at 34-35 degrees C by changing the aerating gas from 95% O2-5% CO2 to 95% N2-5% CO2. Field potential (FP) and intracellular recordings were obtained in layers II/III of primary somatosensory cortex. Intracellular injection of biocytin revealed the characteristic morphology of supragranular spiny pyramidal neurons. 2. Excitatory synaptic transmission reversibly decreased by 45% as estimated from FP responses to orthodromic stimulation of the underlying white matter/layer VI. Excitatory postsynaptic potentials (EPSPs) were suppressed by 36% in amplitude and recovered within 2-3 min after reoxygenation. During the recovery period, EPSPs showed a reversible increase in duration by 72%. 3. Inhibitory synaptic transmission was completely blocked as determined in FP responses with a paired-pulse inhibition protocol. The fast inhibitory postsynaptic potential (IPSP) declined by 58% during hypoxia. The long-lasting IPSP was suppressed by 75% and showed incomplete recovery. During hypoxia, the amplitude of both IPSPs was significantly more strongly suppressed than the EPSP. 4. In 40% of the cells, hypoxia induced an early anoxic hyperpolarization with a reversal potential of E = -80.8 mV, followed by a postanoxic hyperpolarization (E = -89.4 mV). In a second group of cells (37%), a gradual anoxic depolarization with E = -57.5 mV was observed instead of an early hyperpolarization. In both groups of cells, the anoxic response was associated with a marked decrease in input resistance, by 42 and 31%, respectively. 5. The spike discharge frequency was reversibly suppressed by 71% during hypoxia. A transient hyperexcitability accompanied with a rise in input resistance and discharge rate was observed in 38% of the cells on reoxygenation. 6. The reversal potential of the anoxic hyperpolarization was unaffected by tetrodotoxin (TTX) but was significantly altered by application of the ATP-sensitive K+ channel (KATP) blocker gliquidone. Application of gliquidone additionally resulted in a significantly smaller hypoxia-induced decline in paired-pulse inhibition. 7. Increases in tissue high-energy phosphates induced by preincubating the slices in 25 mM creatine for greater than 2 h had a pronounced protective effect on excitatory and inhibitory synaptic transmission. 8. These data suggest a selective vulnerability of the neocortical inhibitory system during hypoxia. Our results further indicate that hypoxia activates a pre- and postsynaptic KATP conductance because of the decline in intracellular ATP.
Luhmann
H J
HJ
Institute of Neurophysiology, University of Cologne, Federal Republic of Germany.
Heinemann
U
U
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003401:Creatine / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; C010969:gliquidone; D003401:Creatine