Hypoxic excitability changes and sodium currents in hippocampus CA1 neurons.
1. The objective of the present study was to distinguish if inhibition of neuronal activity by hypoxia is related to a block of voltage-gated Na+ channels. 2. The effect of chemical hypoxia induced by cyanide (0.5 mM, 10 min perfusion) was studied with patch-clamp technique in visualized intact CA1 pyramidal neurons in rat brain slices. Action potentials were elicited in whole cell current-clamp recordings and the threshold was estimated by current pulses of 50-ms duration and incremental amplitudes (n = 31). The effect of cyanide on the Na+ current and conductance was studied in voltage clamp recordings from cell-attached patches (n = 13). 3. Cyanide perfusion during 10 min increased the threshold for excitation by 73 +/- 79 pA (p = 0.001), which differed from the effect in control cells (11 +/- 41 pA, ns). The change in current threshold was correlated to a change in membrane potential (r = -0.88, p < 0.0001). Cyanide had no significant effect on the peak amplitude, duration, or rate of rise of the action potential. 4. Cyanide perfusion did not change the Na+ current size, but caused a small decrease in ENa (-17 +/- 22 mV, ns) and a slight increase in Na+ conductance (+14 +/- 26%, ns), which differed (p = 0.045) from controls (-19 +/- 23 %, ns). 5. In conclusion, chemical hypoxia does not cause a decrease in Na+ conductance. The decreased excitability during hypoxia can be explained by an increase in the current threshold, which is correlated with the effect on the membrane potential.
Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm, Sweden. marita.englund@ks.se
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M
Englund
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M
Bjurling
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F
Edin
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Hyllienmark
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Brismar
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D003486:Cyanides / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*
D003486:Cyanides; D015222:Sodium Channels