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Hypoxic Excitability Changes and Sodium Currents in Hippocampus CA1 Neurons

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Abstract

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 E Na (−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.

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Authors and Affiliations

  1. Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm, Sweden

    M. Englund, M. Bjurling, F. Edin, L. Hyllienmark & T. Brismar

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  1. M. Englund
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  2. M. Bjurling
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  3. F. Edin
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  4. L. Hyllienmark
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  5. T. Brismar
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Englund, M., Bjurling, M., Edin, F. et al. Hypoxic Excitability Changes and Sodium Currents in Hippocampus CA1 Neurons. Cell Mol Neurobiol 24, 685–694 (2004). https://doi.org/10.1023/B:CEMN.0000036405.53992.78

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