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

Abstract

AbstractCartwheel neurons from the dorsal cochlear nucleus (DCN) are glycinergic interneurons and the primary source of inhibition on the fusiform neurons, the principal excitatory neuron in the DCN. Most cartwheel neurons present spontaneous firing (active neurons), producing a steady inhibitory tone on fusiform neurons. In contrast, a smaller fraction does not fire spontaneously (quiet neurons). Additionally, hyperactivity of fusiform neurons is seen in animals with behavioral evidence of tinnitus. Due to its relevance in controlling the excitability of fusiform neurons, we investigated the ion channels responsible for the spontaneous firing of cartwheel neurons. We found that quiet neurons express an outward conductance not seen in active neurons, which generates a stable resting potential. This current was sensitive to tolbutamide, an ATP-sensitive potassium channel (KATP) antagonist. After its inhibition, quiet neurons start to fire spontaneously, while the behavior of active neurons was not affected. On the other hand, in active neurons, KATP agonist diazoxide activated a conductance similar to the KATP conductance of quiet neurons and stopped spontaneous firing. According to the effect of KATP channels on CW neuron firing, glycinergic neurotransmission in DCN was increased by tolbutamide and decreased by diazoxide. Finally, slices incubated with the tinnitus-inducing agent sodium salicylate presented more quiet neurons expressing the KATP conductance, which increased the proportion of quiet neurons. Our results reveal an unexpected role of KATP channels in controlling the spontaneous firing of neurons. Additionally, changes in KATP channel activity of cartwheel neurons can be related to the DCN hyperactivity seen in tinnitus.