The Role of Kv1.2-Containing Potassium Channels in Serotonin-Induced Glutamate Release from Thalamocortical Terminals in Rat Frontal Cortex
Evelyn K. Lambe, George K. Aghajanian
Journal of Neuroscience December 15, 2001 DOI: 10.1523/jneurosci.21-24-09955.2001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat prefrontal cortex brain slices |
| Interventions | serotonin 4-aminopyridine α-dendrotoxin tetrodotoxin ω-agatoxin-IVA μ-opiates |
| Topics | Serotonin |
| Keywords | Glutamate receptor Potassium channel Channel blocker Tetrodotoxin Pharmacology Biophysics |
| Citations | 111 |
| Key findings | Blockade of Kv1.2-containing potassium channels is part of the mechanism by which serotonin induces glutamate release from thalamocortical terminals. |
Abstract
Serotonin 5-HT 2A receptors have been implicated in psychiatric illness and the psychotomimetic effects of hallucinogens. In brain slices, focal stimulation of 5-HT 2A 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 α-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 ω-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.
Comparable studies
Other experimental studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Rat brain | 1997 | Experimental study |
Citations in the library
Cited by 17
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- Lysergic acid diethylamide and [−]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex Brain Research August 27, 2004
- Salvinorin A fails to substitute for the discriminative stimulus effects of LSD or ketamine in Sprague-Dawley rats. Pharmacology, Biochemistry, and Behavior September 1, 2010
- Metabotropic Glutamate2 Receptors Play a Key Role in Modulating Head Twitches Induced by a Serotonergic Hallucinogen in Mice Frontiers in Pharmacology March 15, 2018
- Cellular rules underlying psychedelic control of prefrontal pyramidal neurons bioRxiv (Cold Spring Harbor Laboratory) October 23, 2023
and 12 more in the library
Cites 5
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release Brain Research April 1, 1999
- DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons Journal of Neuroscience December 1, 2000
- Blood Flow and Cerebral Laterality in the Mescaline Model of Psychosis Pharmacopsychiatry July 1, 1998
- Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology May 1997