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.
Shi
Xue-Ru
XR
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
Chang
Jing
J
Ding
Jian-Hua
JH
Fan
Yi
Y
Sun
Xiu-Lan
XL
Hu
Gang
G
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