Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones

Trevor Bushell, Catherine Clarke, Alistair Mathie, Brian Robertson

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

1. Whole-cell patch clamp recordings were used to investigate the properties of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones at a holding potential of -20 mV. 2. Increasing the external potassium (K+) concentration from 3 mM to 20 mM produced a rightward shift in the observed reversal potential of ∼30 mV or ∼40 mV for a K+-or a caesium (Cs+)-based intracellular solution respectively, indicating the outward current was a K+ current. 3. The outward current was partially inhibited by the K+ channel blocker, tetraethylammonium (TEA; IC50=0.15 mM). Subsequently, the background or TEA-insensitive current was measured in the presence of 1 mM TEA. 4. The background current was reversibly inhibited by barium (Ba2+; 300 μM, 50%) and potentiated by the application of arachidonic acid (AA; 1 mM, 62%). 5. The volatile anaesthetic, halothane (1 mM), and the neuroprotectant, riluzole (500 μM), both reversibly inhibited the background current by 54% and 36% respectively. 6. The background current was insensitive to changes in both intracellular and extracellular acidification. 7. The GABAB and μ-opioid receptor agonists, baclofen and [D-Ala2, N-MePhe4-Gly-ol5] enkephalin (DAMGO) both reversibly potentiated the outward current by 42% and 26% respectively. In contrast, the metabotropic glutamate receptor and acetylcholine receptor agonists, (S)-3,5-dihydroxyphenylglycine (DHPG) and muscarine both reversibly inhibited the outward current by 48% and 42% respectively. 8. These data suggest that cerebellar Purkinje neurones possess a background current which shares several properties with recently cloned two-pore K+ channels, particularly THIK-1.

Original languageEnglish
Pages (from-to)705-712
Number of pages8
JournalBritish Journal of Pharmacology
Volume135
Issue number3
DOIs
Publication statusPublished - 28 Feb 2002

Keywords

  • cerebellum
  • G-protein
  • modulation
  • non-inactivating current
  • Purkinje
  • two-pore potassium channel

Cite this