Beta-phenylethylamine inhibits K+ currents in neocortical neurons of the rat: a possible mechanism of beta-phenylethylamine-induced seizures.

Abstract

beta-Phenylethylamine (beta-PEA), an endogenous amine synthesized in the brain, serves as a neuromodulator and is involved in the pathophysiology of various neurological disorders such as depression, schizophrenia, and attention-deficit hyperactivity disorder. beta-PEA fully exerts the physiological effects within the nanomolar concentration range via the trace amine receptors, but beta-PEA also causes convulsions at much higher concentrations via an as yet unknown mechanism. To investigate the electrophysiological mechanism by which beta-PEA induces convulsions, we examined the effect of beta-PEA on ionic currents passing through the cell membrane of dissociated rat cerebral cortical neurons, using a patch-clamp technique. The external application of beta-PEA suppressed ionic currents which continuously flowed when the membrane potential was held at -25 mV. The suppression was in a concentration-dependent manner and a half-maximal effective concentration was 540 muM. These currents suppressed by beta-PEA consisted of two K(+) currents: a time- and voltage-dependent K(+) current (M-current) and a leakage K(+) current. The suppression of the M-current reduces the efficacy of the current in limiting excessive neuronal firing, and the suppression of the leakage K(+) current can cause membrane depolarization and thus promote neuronal excitation. Reducing both of these currents in concert may produce neuronal seizing activity, which could conceivably underlie the convulsions induced by high-dose beta-PEA.

• Authors: Taro Kitamura, Mitsutoshi Munakata, Kazuhiro Haginoya, Shigeru Tsuchiya, Kazuie Iinuma
• Journal: The Tohoku journal of experimental medicine (Tohoku J Exp Med) Vol. 215 Issue 4 Pg. 333-40 (Aug 2008) ISSN: 1349-3329 [Electronic] Japan
• PMID: 18679007 (Publication Type: Journal Article)

Chemical References

• Phenethylamines
• Potassium Channels
• Psychotropic Drugs
• phenethylamine

Topics

• Animals
• Dose-Response Relationship, Drug
• In Vitro Techniques
• Membrane Potentials (drug effects, physiology)
• Models, Biological
• Neocortex (drug effects, physiology)
• Neurons (drug effects, physiology)
• Phenethylamines (adverse effects, pharmacology)
• Potassium Channels (drug effects)
• Psychotropic Drugs (adverse effects)
• Rats
• Rats, Wistar
• Seizures (chemically induced)