Kir6.2 knockout alters neurotransmitter release in mouse striatum: an in vivo microdialysis study.
ATP-sensitive potassium (K-ATP) channels have been demonstrated to play important roles in the brain. In the present study, Kir6.2 knockout (Kir6.2-/-) mice were used to examine the contribution of Kir6.2-containing K-ATP channels to the regulation of neurotransmitter release via in vivo microdialysis studies. The results showed that the extracellular levels of monoamine and amino acid neurotransmitters in Kir6.2-/- mouse striatum were similar to those in Kir6.2+/+ mice under basal conditions. After high K+ (100mM) perfusion, the extracellular levels of DA and amino acids were increased in both genotypes. These increases, however, were significantly lower in Kir6.2-/- mice than those in Kir6.2+/+ mice. Extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC), a major metabolite of DA, were increased in Kir6.2-/- mice but decreased in Kir6.2+/+ mice in response to high K+ stimulus. The releases of 4-hydroxy-3-methoxy-phenylacetic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were attenuated to a similar extent in both mouse genotypes. Taken together, this study provides direct in vivo evidence that Kir6.2-containing K-ATP channels play regulatory roles in neurotransmitter release in the striatum.
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
Xue-Ru
XR
Shi
Jing
J
Chang
Jian-Hua
JH
Ding
Yi
Y
Fan
Xiu-Lan
XL
Sun
Gang
G
Hu
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis / Q000379:methods; D018377:Neurotransmitter Agents / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency*; D011189:Potassium Chloride / Q000494:pharmacology; D000099161:Kcnj11 Channel
D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid; D018377:Neurotransmitter Agents; D024661:Potassium Channels, Inwardly Rectifying; D011189:Potassium Chloride; D000099161:Kcnj11 Channel