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The Journal of Neuroscience, December 15, 2001, 21(24):9955-9963
The Role of Kv1.2-Containing Potassium Channels in
Serotonin-Induced Glutamate Release from Thalamocortical Terminals in
Rat Frontal Cortex
Evelyn K.
Lambe and
George K.
Aghajanian
Interdepartmental Neuroscience Program and Departments of
Psychiatry and Pharmacology, Yale University School of Medicine, New
Haven Connecticut 06508
Serotonin 5-HT2A receptors have been implicated in
psychiatric illness and the psychotomimetic effects of hallucinogens.
In brain slices, focal stimulation of 5-HT2A receptors in
rat prefrontal cortex results in dramatically increased glutamate
release onto layer V pyramidal neurons, as measured by an increase in
"spontaneous" (nonelectrically evoked) EPSCs. This glutamate
release is blocked by tetrodotoxin (TTX) and is thought to involve
local spiking in thalamocortical axon terminals; however, the detailed
mechanism has remained unclear.
Here, we investigate parallels in EPSCs induced by either serotonin or
the potassium channel blockers 4-aminopyridine (4-AP) or
 -dendrotoxin (DTX). DTX, a selective blocker of Kv1.1-, Kv1.2-, and
Kv1.6-containing potassium channels, has been shown to release glutamate in cortical synaptosomes, presumably by inhibiting a subthreshold-activated, slowly inactivating potassium conductance. By
comparing DTX with other potassium channel blockers, we found that the
ability to induce EPSCs in cortical pyramidal neurons depends on
affinity for Kv1.2 subunits. DTX-induced EPSCs are similar to
5-HT-induced EPSCs in terms of sensitivity to TTX and  -agatoxin-IVA
(a blocker of P-type calcium channels) and laminar selectivity. The
involvement of thalamocortical terminals in DTX-induced EPSCs was
confirmed by suppression of these EPSCs by µ-opiates and thalamic
lesions. More directly, DTX-induced EPSCs substantially occlude those
induced by 5-HT, suggesting a common mechanism of action. No occlusion
by DTX was seen when EPSCs were induced by a nicotinic mechanism. These
results indicate that blockade of Kv1.2-containing potassium channels
is part of the mechanism underlying 5-HT-induced glutamate release from
thalamocortical terminals.
Key words:
K+; voltage-gated; dendrotoxin; 5-hydroxytryptamine; 5-HT2A receptor; psychedelic
hallucinogens; 4-aminopyridine; prefrontal
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249955-09$05.00/0
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