Differential actions of AMP kinase on ATP‐sensitive K+ currents in ventral tegmental area and substantia nigra zona compacta neurons

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.