Group i mGluRs evoke K-ATP current by intracellular Ca2+ mobilization in rat subthalamus neurons

Ke Zhong Shen, Steven W. Johnson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


We reported previously that Ca2+ influx through N-methly-Daspartate-gated channels evokes ATP-sensitive K+ (K-ATP) currents in rat subthalamic nucleus (STN) neurons. By using whole-cell patch clamp recordings in brain slices, we investigated the ability of (RS)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR) agonist, to evoke K-ATP currents. DHPG (20 μM) evoked outward current at 270 mV and was associated with a positive slope conductance of 2.7 nS. The sulfonylurea agent tolbutamide (100 mM) converted the positive slope to negative slope conductance, indicating mediation by K-ATP channels (ATPsensitive K+ channels). Currents evoked by DHPG were significantly reduced by a combination of mGluR1 and mGluR5 negative allosteric modulators. DHPG-evoked outward current was blocked by cyclopiazonic acid and thapsigargin and mimicked by caffeine, suggesting mediation by release of intracellular Ca2+. DHPG outward current was also blocked by ryanodine and 2-aminoethoxydiphenylborane, suggesting mediation by ryanodine- and inositol 1,4,5-triphosphate-sensitive Ca2+ release. The nitric oxide synthase inhibitor NG-nitro-Larginine methyl ester and inhibitors of protein kinase G activity also suppressed DHPG-induced outward current. Voltage recordings showed that tolbutamide prolonged depolarizing plateau potentials and increased the spontaneous firing rate of STN neurons recorded in the presence of DHPG. These results show that group I mGluR stimulation generates K-ATP current by a nitric oxide- and protein kinase G-dependent process that is mediated by release of Ca2+ from intracellular stores. Because burst firing is linked to symptoms of Parkinson's disease, we suggest that K-ATP channels might provide a physiologically important inhibitory influence on STN neuronal activity.

Original languageEnglish (US)
Pages (from-to)139-150
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
StatePublished - Apr 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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