Diversity of Neuron-specific K+-Cl−Cotransporter Expression and Inhibitory Postsynaptic Potential Depression in Rat Motoneurons

Tsuyoshi Ueno,Akihito Okabe,Norio Akaike,Atsuo Fukuda,Junichi Nabekura

doi:10.1074/jbc.m109439200

Tsuyoshi Ueno, Akihito Okabe + Show 3 more

Open Access

https://doi.org/10.1074/jbc.m109439200

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Abstract

Motoneurons receive a robust recurrent synaptic inhibition by gamma-aminobutyric acid and glycine, which activate Cl(-) channels. Thus, Cl(-) homeostasis determines the efficacy of synaptic inhibition in the motoneurons. In situ hybridization reveals that the neuronal K(+)-Cl(-) cotransporter isoform 2 (KCC2), a major mechanism in maintaining a low Cl(-) concentration in neurons, is abundantly expressed in the facial, hypoglossal (XII), and spinal motoneurons innervating striated muscle, whereas the dorsal vagal motoneurons (DMVs) controlling smooth muscle exhibited little expression of KCC2. This raises a general interest in the correlation between KCC2 expression and inhibitory postsynaptic potential (IPSP) performance in the native circuits. Intracellular and whole-cell patch recordings revealed that an activity-dependent depression of IPSPs and positive shift of IPSP reversal potentials were more prominent in the DMV than in the XII. Cl(-) influx through Cl(-) channels was extruded more potently in the XII than in the DMV, suggesting that differences in Cl(-) extrusion account for these dynamic differences of IPSP. Cl(-) extrusion was inhibited by either furosemide or an increase in extracellular potassium concentrations. Thus, the rigid maintenance of IPSP and rapid Cl(-) extrusion in the XII reflects an intense expression of KCC2. KCC2 expression may strongly influence the IPSP depression and functional properties of the motoneurons innervating striated muscles.

Highlights

Motoneurons receive a robust recurrent synaptic inhibition by ␥-aminobutyric acid and glycine, which activate Cl؊ channels
This raises a general interest in the correlation between K؉-Cl؊ cotransporter isoform 2 (KCC2) expression and inhibitory postsynaptic potential (IPSP) performance in the native circuits
We evaluated the differences in GABAergic IPSP performance in two groups of motoneurons, one innervating striated muscle and the other controlling smooth muscle, and compared their [ClϪ]i regulation

Summary

Introduction

Motoneurons receive a robust recurrent synaptic inhibition by ␥-aminobutyric acid and glycine, which activate Cl؊ channels. Across these two pools of motoneurons, we found a close correspondence between differences in their ClϪ transport properties and activity-dependent IPSP depression along with their KCC2 expression. To examine whether the diversity of KCC2 expression correlates with the difference in ClϪ homeostasis and IPSP performance between the two sets of motor neurons, electrophysiological approaches were employed on XII neurons and the DMV.

Results

Conclusion