The potassium channel KCNQ5/Kv7.5 is localized in synaptic endings of auditory brainstem nuclei of the rat

Abstract

KCNQ, also called Kv7, is a family of voltage-dependent potassium channels with important roles in excitability regulation. Of its five known subunits, KCNQ5/Kv7.5 is extensively expressed in the central nervous system and it contributes to the generation of M-currents. The distribution of KCNQ5 was analyzed in auditory nuclei of the rat brainstem by high-resolution immunocytochemistry. Double labeling with anti-KCNQ5 antibodies and anti-synaptophysin or anti-syntaxin, which mark synaptic endings, or anti-microtubule-associated protein 2 (MAP2) antibodies, which mark dendrites, were used to analyze the subcellular distribution of KCNQ5 in neurons in the cochlear nucleus, superior olivary complex, nuclei of the lateral lemniscus, and inferior colliculus. An abundance of KCNQ5 labeling in punctate structures throughout auditory brainstem nuclei along with colocalization with such synaptic markers suggests that a preferred localization of KCNQ5 is in synaptic endings in these auditory nuclei. Punctate KCNQ5 immunoreactivity virtually disappeared from the cochlear nucleus after cochlea removal, which strongly supports localization of this channel in excitatory endings of the auditory nerve. Actually, neither glycinergic endings, labeled with an anti-glycine transporter 2 (GlyT2) antibody, nor gamma-aminobutyric acid (GABA)ergic endings, labeled with an anti-glutamic acid decarboxylase (GAD65) antibody, contained KCNQ5 immunoreactivity, suggesting that KCNQ5 is mostly in excitatory endings throughout the auditory brainstem. Overlap of KCNQ5 and MAP2 labeling indicates that KCNQ5 is also targeted to dendritic compartments. These findings predict pre- and postsynaptic roles for KCNQ5 in excitability regulation in auditory brainstem nuclei, at the level of glutamatergic excitatory endings and in dendrites.