C2 hemisection shifts the balance of KCC2 and NKCC1 expression in phrenic motoneurons

In adult mammals, GABA and Glycine are major inhibitory neurotransmitters. Their physiological effect is determined by cellular chloride homeostasis, which depends on chloride co‐transporter activity. During early development, type 1 sodium‐potassium chloride‐co‐transporter (NKCC1) induces high intracellular chloride concentrations, causing excitatory GABA/Glycine effects. In mature neurons, low intracellular chloride concentrations result from increased type 2 potassium chloride‐co‐transporter (KCC2) expression. Thus, the KCC2/NKCC1 balance is a critical determinant of neuronal responses to GABA/Glycine. Altered chloride homeostasis from increases in the KCC2/NKCC1 balance may cause hyper‐excitability, leading to (for example) chronic pain or spasticity after spinal injury. Here we studied KCC2 and NKCC1 expression via immunohistochemitry in retrogradely labeled phrenic motoneurons (cholera toxin B fragment) of adult rats before and after C2 cervical hemisection. KCC2 and NKCC1 protein were detected in cell bodies and possibly dendrites of sham rats. C2 hemisection down‐regulated KCC2 and up‐regulated NKCC1. Thus, C2 hemisection may alter chloride homeostasis and degrade inhibitory regulation of phrenic motoneuron activity. These effects may increase phrenic motoneuron excitability, increasing their output for a given excitatory synaptic input following spinal injury.