Decreases in metabolic ATP open KATP channels and reduce firing in an auditory brainstem neuron: A dynamic mechanism of firing control during intense activity

Autor(es)

de Siqueira, Daniela Vanessa F. ; Boaretto, Natalia ; Leao, Ricardo Mauricio

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience; v. 564, p. 8-pg., 2025-01-09.

Resumo

Cartwheel (CW) neurons are glycinergic interneurons in the dorsal cochlear nucleus (DCN) that exhibit spontaneous firing, resulting in potent tonic inhibition of fusiform neurons. CW neurons expressing open ATPsensitive potassium (KATP) channels do not fire spontaneously, and activation of KATP channels halts spontaneous firing in these neurons. However, the conditions that regulate KATP channel opening in CW neurons remain unknown. Here, we tested the hypothesis that fluctuations in metabolic ATP levels modulate KATP channels in CW neurons. Using whole-cell patch-clamp recordings in CW neurons from young rat brain slices (p17-22) with an ATP-free internal solution, we observed that the mitochondrial uncoupler CCCP hyperpolarized the membrane potential, reduced spontaneous firing, and generated an outward current, which was inhibited by the KATP channel antagonist tolbutamide. Additionally, a glucose-free external solution quickly activated KATP channels and ceased spontaneous firing. We hypothesized that intense membrane ion ATPase activity during strong depolarization would deplete intracellular ATP, leading to KATP channel opening. Consistent with this, depolarizing CW neurons with a 250 pA DC did not increase spontaneous firing because the depolarization activated KATP channels; however, the same depolarization after tolbutamide administration increased firing, suggesting that ATP depletion triggered KATP channel opening to limit action potential firing. These results indicate that KATP channels in the DCN provide dynamic control over action potential firing, preventing excessive excitation during high-firing activity. (AU)

• Processo FAPESP: 22/14196-3 - Canais de potássio sensíveis ao ATP no controle da excitabilidade neuronal
• Beneficiário: Ricardo Mauricio Xavier Leão
• Modalidade de apoio: Auxílio à Pesquisa - Regular