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

Abstract

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) in stellate cells of the ventral cochlear nucleus. Subunits of K 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 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 HO (0.88 mM) induced marked responses in stellate cells, characterized by membrane hyperpolarization which were blocked by K antagonists. Blockers of K 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 channels seemed to be composed dominantly of Kir 6.2 subunit and SUR1 and SUR2 and activation or inhibition of K channels regulates firing properties of stellate cells by means of influencing resting membrane potential and input resistance.

ATP‐sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem

“…A recent report showed active K ATP channels in stellate cells of the ventral cochlear nucleus (Bal et al . 2018). We therefore tested if K ATP channels could cause the difference in the K ir currents in quiet neurons.…”

“…Interestingly, a recent report showed the presence of K ATP channels in the stellate cells from the ventral cochlear nucleus (Bal et al . 2018), suggesting that these channels can be relevant for the control of membrane potential and AP firing in other auditory brainstem neurons.…”

“…More studies on the sensitivity of the K ATP currents of CW neurons to their metabolic status would be necessary to know if their activity relates to the energetic demands of the neuron. Interestingly, a recent report showed the presence of K ATP channels in the stellate cells from the ventral cochlear nucleus (Bal et al 2018), suggesting that these channels can be relevant for the control of membrane potential and AP firing in other auditory brainstem neurons.…”

“…K ATP channels are produced by the subunits Kir6.2 or 6.1, together with a sulphonylurea receptor SUR1 or SUR2, expressed in several central regions (Karschin et al 1997;Dunn-Meynell, 1998;Zhou et al 1999Zhou et al , 2002. A recent report showed active K ATP channels in stellate cells of the ventral cochlear nucleus (Bal et al 2018). We therefore tested if K ATP channels could cause the difference in the K ir currents in quiet neurons.…”

Extracranial activation of ATP-sensitive potassium channels induces vasodilation without nociceptive effects

“…In rats, extracellular application of KCOs cromakalim (a less potent form of levcromakalim) and diazoxide caused hyperpolarization in neurons isolated from the midbrain and sensory neurons, respectively (3,24). This hyperpolarizing effect can be reversed by the K ATP channel blocker tolbutamide (25). We used one of the most potent KCOs (26) with a dose of 150 µg/ml (524 µM), which should be sufficient to induce hyperpolarization in the surrounding tissue.…”