Elsevier

Brain Research

Volume 362, Issue 2, 8 January 1986, Pages 271-280
Brain Research

Frequency-dependent action of phenytoin on lamprey spinal axons

https://doi.org/10.1016/0006-8993(86)90451-8Get rights and content
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Abstract

The effect of the antiepileptic drug phenytoin (diphenylhydantoin, DPH) was tested on the conduction of intracellularly recorded action potentials in lamprey giant reticulospinal axons. When the isolated spinal cord was exposed to 80 μM DPH for up to 4 h, no significant effect was seen on the amplitude or conduction velocity of the action potential, although the maximum rate of rise was reduced from 247.8 to 149.6 V/s after 1 h. However, at higher stimulus frequencies both the amplitude and conduction velocity of the action potential were reduced progressively during a 500 stimulus train. The reduction was greater the higher the stimulus frequency, and was reversed upon return to 1 Hz stimulation. At frequencies greater than 40 Hz an all-or-none block developed. This also developed sooner the higher the stimulus frequency. Axons bathed in drug-free solutions did not show this effect at stimulus frequencies up to 100 Hz. Similar effects were seen in 16 μM DPH when the spinal cord was exposed to the drug overnight. This is close to the human therapeutic CSF level. The frequency-dependent depression of the action potential was greatly potentiated by increasing the extracellular potassium concentration from 2.1 to 5 mM. Under these conditions the axons rapidly developed block at stimulus frequencies as low as 2 Hz, and this was not reversible during a 5 h wash. In the absence of DPH, 5 mM potassium produced a 4–5 mV depolarization, but did not induce a frequency-dependent block. This effect of potassium may be important to the therapeutic effect of DPH because during epileptiform activity the extracellular K+ increases several fold.

Keywords

phenytoin
lamprey
spinal cord
axon
action potential
frequency-dependence
potassium

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