Dendrotoxin sensitive potassium channels modulate GABA but not glutamate release in the rat entorhinal cortex in vitro.
We have previously shown that the anticonvulsant drug, phenytoin, increases the frequency and amplitude of spontaneous inhibitory postsynaptic currents at GABA synapses on principal neurones in the rat entorhinal cortex. This effect is similar to that seen at other GABA synapses following blockade of voltage-gated potassium channels (Kv1.1, 1.2 and 1.6) with alpha-dendrotoxin. In the present study we examined whether dendrotoxins can alter GABA release at synapses in the entorhinal cortex. We recorded spontaneous inhibitory postsynaptic currents using whole cell voltage clamp techniques in slices of rat entorhinal cortex in vitro. alpha-Dendrotoxin evoked an increase in frequency and amplitude of spontaneous inhibitory postsynaptic currents, an effect that was blocked by prior perfusion with tetrodotoxin. The effect of the toxin did not occlude the increase in spontaneous inhibitory postsynaptic currents seen with phenytoin. Indeed, the effect of the two drugs together was, at least, additive on GABA release. Perfusion with the specific Kv1.1 blocker, dendrotoxin-K had no effect on GABA release. In addition, alpha-dendrotoxin had no effect on frequency or amplitude of spontaneous excitatory postsynaptic currents at glutamate synapses on entorhinal cortex neurones. We conclude that K-channels containing the Kv1.2 and/or 1.6 subunits modulate the release of GABA, but not glutamate in the entorhinal cortex. The modulation of GABA release by phenytoin is unlikely to be due to an effect on these channels.
Cunningham
M O
MO
Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, BS8 1TD, Bristol, UK.
Jones
R S
RS
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology*; D018728:Entorhinal Cortex / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D004546:Elapid Venoms; D009498:Neurotoxins; D010455:Peptides; D015221:Potassium Channels; C081506:dendrotoxin K; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; C020273:dendrotoxin