1. Differential actions of AMP kinase on ATP-sensitive K+currents in ventral tegmental area and substantia nigra zona compacta neurons
- Author
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Yan Na Wu, Steven W. Johnson, and Ke Zhong Shen
- Subjects
0301 basic medicine ,ATP-sensitive potassium channel ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,AMPK ,Substantia nigra ,Biology ,Ventral tegmental area ,Midbrain ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,nervous system ,Dopamine ,mental disorders ,medicine ,Diazoxide ,Patch clamp ,Neuroscience ,psychological phenomena and processes ,030217 neurology & neurosurgery ,medicine.drug - Abstract
ATP-sensitive K+ (K-ATP) channels play significant roles in regulating the excitability of dopamine neurons in the substantia nigra zona compacta (SNC). We showed previously that K-ATP channel function is up-regulated by AMP-activated protein kinase (AMPK). This study extended these studies to the neurons adjacent to the SNC in the ventral tegmental area (VTA). Using patch pipettes to record whole-cell currents in slices of rat midbrain, we found that the AMPK activator A769662 increased the amplitude of currents evoked by the K-ATP channel opener diazoxide in presumed dopamine-containing VTA neurons. However, current evoked by diazoxide with A769662 was significantly smaller in VTA neurons compared to SNC neurons. Moreover, a significantly lower proportion of VTA neurons responded to diazoxide with outward current. However, A769662 was able to increase the incidence of diazoxide-responsive neurons in the VTA. In contrast, A769662 did not potentiate diazoxide-evoked currents in presumed non-dopamine VTA neurons. These results show that AMPK activation augments K-ATP currents in presumed dopamine neurons in the VTA and SNC, although diazoxide-evoked currents remain less robust in the VTA. We conclude that K-ATP channels may play important physiological roles in VTA and SNC dopamine neurons.
- Published
- 2017