TY - JOUR
T1 - Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones
AU - Bushell, Trevor
AU - Clarke, Catherine
AU - Mathie, Alistair
AU - Robertson, Brian
PY - 2002/2/28
Y1 - 2002/2/28
N2 - 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.
AB - 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.
KW - cerebellum
KW - G-protein
KW - modulation
KW - non-inactivating current
KW - Purkinje
KW - two-pore potassium channel
UR - http://www.scopus.com/inward/record.url?scp=0036181995&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0704518
DO - 10.1038/sj.bjp.0704518
M3 - Article
C2 - 11834618
AN - SCOPUS:0036181995
SN - 0007-1188
VL - 135
SP - 705
EP - 712
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 3
ER -