Distribution and phenotype of neurons containing the ATP-sensitive K+ channel in rat brain

Abstract

Select groups of neurons within the brain alter their firing rate when ambient glucose levels change. These glucose-responsive neurons are integrated into systems which control energy balance in the body. They contain an ATP-sensitive K+ channel (KATP) which mediates this response. KATP channels are composed of an inwardly rectifying pore-forming unit (Kir6.1 or Kir6.2) and a sulfonylurea binding site. Here, we examined the anatomical distribution and phenotype of cells containing Kir6.2 mRNA within the rat brain by combinations of in situ hybridization and immunocytochemistry. Cells containing Kir6. 2 mRNA were widely distributed throughout the brain without apparent concentration in areas known to contain specific glucose-responsive neurons. Kir6.2 mRNA was present in neurons expressing neuron-specific enolase, tyrosine hydroxylase, neuropeptide Y (NPY) and the glutamic acid decarboxylase isoform, GAD65. No astrocytes expressing glial fibrillary acidic protein or oligodendrocytes expressing carbonic anhydrase II were found to co-express Kir6.2 mRNA. Virtually all of the NPY neurons in the hypothalamic arcuate n. and catecholamine neurons in the substantia nigra, pars compacta and locus coeruleus contained Kir6.2 mRNA. Epinephrine neurons in the C2 area also expressed high levels of Kir6.2, while noradrenergic neurons in A5 and A2 areas expressed lower levels. The widespread distribution of Kir6.2 mRNA suggests that the KATP channel may serve a neuroprotective role in neurons which are not directly involved in integrating signals related to the body's energy homeostasis.