NMDA enhances a depolarization-activated inward current in subthalamic neurons

Zi Tao Zhu, Adam Munhall, Ke Zhong Shen, Steven W. Johnson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Previous studies have shown that N-methyl-d-aspartate (NMDA) receptor stimulation evokes Ca2+- and Na+-dependent burst firing in subthalamic nucleus (STN) neurons. Using whole-cell patch pipettes to record currents under voltage-clamp, we identified a time-dependent depolarization-activated inward current (DIC) that may underlie NMDA-induced burst firing in STN neurons in rat brain slices. Continuous superfusion with NMDA (20 μM) elicited a marked TTX-insensitive inward current when the membrane was depolarized to the level of -70 or -50 mV, from a holding potential of -100 mV. This current had a long duration, and its peak amplitude occurred at a test potential of -60 mV. DIC could not be evoked using the non-NMDA receptor agonist d,l-α-amino-3-hydroxy-5-methylisoxalone-4-propionic acid (AMPA). DIC was blocked by either intracellular BAPTA or by removal of extracellular Ca2+, but selective blockers of T-type (mibefradil), L-type (nifedipine) and N-type (ω-conotoxin GVIA) Ca2+ channels did not. Perfusing slices with a low extracellular concentration of sodium abolished the NMDA-induced DIC, implying that both Ca2+ and Na + are necessary for the expression of DIC. Transient receptor potential (TRP) channel blockers flufenamic acid and SKF96365 severely reduced DIC amplitude, whereas NMDA-gated currents were either increased or were unchanged. These results suggest that the activation of NMDA receptors enhances a Ca2+-activated non-selective cation current that may be mediated by a member of the TRP channel family in STN neurons.

Original languageEnglish (US)
Pages (from-to)317-327
Number of pages11
JournalNeuropharmacology
Volume49
Issue number3
DOIs
StatePublished - Sep 1 2005

Keywords

  • Ca -activated non-selective cation current
  • Depolarization
  • NMDA
  • Subthalamic nucleus
  • Whole-cell voltage clamp

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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