Is Neuronal Inhibition or Excitability Controlled by Na+K+2Cl- Transporters?

The study by Bonalume et al. (2021) investigated the role of Na⁺K⁺2Cl^– transporters, specifically NKCC1, in regulating neuronal excitability and inhibition through GABAA receptor activation in murine sensory nerve fibers. They found that GABA application depolarized axons via GABAA receptors, with excitability dependent on the ß3 subunit. Blocking NKCC1 reduced GABA-induced excitability increases, suggesting NKCC1's role in maintaining high intracellular Cl^– concentrations and depolarizing GABAA currents. The study highlighted a feed-forward link between neuronal activity and excitability, with implications for understanding pain perception and potential medical interventions.