Modulation of Excitability of Stellate Neurons in the Ventral Cochlear Nucleus of Mice by ATP-Sensitive Potassium...

Major voltage-activated ionic channels of stellate cells in the ventral part of cochlear nucleus (CN) were largely characterized previously. However, it is not known if these cells are equipped with other ion channels apart from the voltage-sensitive ones. In the current study, it was aimed to study subunit composition and function of ATP-sensitive potassium channels (K_ATP) in stellate cells of the ventral cochlear nucleus. Subunits of K_ATP channels, Kir6.1, Kir6.2, SUR1, and SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN tissue. The specific and clearly visible bands for all subunits but that for Kir6.1 were seen in Western blot. Using immunohistochemical staining technique, stellate cells were strongly labeled with SUR1 and Kir6.2 antibodies and moderately labeled with SUR2 antibody, whereas the labeling signals for Kir6.1 were too weak. In patch clamp recordings, K_ATP agonists including cromakalim (50 µM), diazoxide (0.2 mM), 3-Amino-1,2,4-triazole (ATZ) (1 mM), 2,2-Dithiobis (5-nitro pyridine) (DTNP) (330 µM), 6-Chloro-3-isopropylamino- 4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NNC 55-0118) (1 µM), 6-chloro-3-(methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NN414) (1 µM), and H₂O₂ (0.88 mM) induced marked responses in stellate cells, characterized by membrane hyperpolarization which were blocked by K_ATP antagonists. Blockers of K_ATP channels, glibenclamide (0.2 mM), tolbutamide (0.1 mM) as well as 5-hydroxydecanoic acid (1 mM), and catalase (500 IU/ml) caused depolarization of stellate cells, increasing spontaneous action potential firing. In conclusion, K_ATP channels seemed to be composed dominantly of Kir 6.2 subunit and SUR1 and SUR2 and activation or inhibition of K_ATP channels regulates firing properties of stellate cells by means of influencing resting membrane potential and input resistance.