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TRPV1 channels regulate cortical excitability in humans.

Francesco Mori1, Michele Ribolsi, Hajime Kusayanagi

  • 1Center for Neurology, Department of Neuroscience, University Tor Vergata, 00133 Rome, Italy.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 21, 2012
PubMed
Summary

Genetic variations in the TRPV1 gene influence human cortical excitability. Specifically, a TRPV1 gene polymorphism (rs222747) enhances glutamate transmission, impacting brain function.

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Area of Science:

  • Neuroscience
  • Human Physiology
  • Genetics

Background:

  • Transient receptor potential vanilloid 1 (TRPV1) channels are known to modulate glutamate release in rodent synapses.
  • Nonsynonymous single-nucleotide polymorphisms (SNPs) in the human TRPV1 gene can alter channel function.
  • Understanding TRPV1's role in human synaptic transmission is crucial for neurological research.

Purpose of the Study:

  • To investigate the impact of TRPV1 genetic polymorphisms on human cortical excitability.
  • To determine if specific TRPV1 SNPs affect synaptic transmission measured by transcranial magnetic stimulation (TMS).

Main Methods:

  • Genotyping of two TRPV1 SNPs (rs222747 and rs222749) in 77 healthy subjects.
  • Assessment of cortical excitability using various TMS paradigms, including single, paired, and repetitive pulses.
  • Evaluation of short-interval intracortical facilitation (SIF) and other TMS-derived measures of cortical inhibition and plasticity.

Main Results:

  • No significant association was found between rs222749 variants and altered cortical responses to TMS.
  • Subjects homozygous for the 'G' allele of rs222747 showed significantly enhanced short-interval intracortical facilitation (SIF).
  • SIF is a measure of glutamate transmission, suggesting enhanced glutamatergic activity in these individuals.

Conclusions:

  • The study provides the first evidence that TRPV1 channels regulate cortical excitability in humans, specifically related to paired-pulse stimulation.
  • The 'G' allele of the TRPV1 SNP rs222747 is associated with increased glutamate transmission in the human motor cortex.
  • TRPV1 genetic variations may play a role in modulating human brain excitability and synaptic function.