Vestibular Role of KCNQ4 and KCNQ5 K+ Channels Revealed by Mouse Models

Abstract

Background: KCNQ K ϩ channels regulate neuronal excitability, and KCNQ4 mutations cause deafness.

Differential Protein Kinase C-dependent Modulation of Kv7.4 and Kv7.5 Subunits of Vascular Kv7 Channels

“…For example, Kv7.2/7.3 and Kv7.5/7.3 heteromeric channels underlie neuronal M-currents (6,8,9). Recently, Kv7.4/Kv7.5 heterotetramers were demonstrated in an expression system based on Förster resonance energy transfer (FRET) and also based on co-expression of dominant-negative mutants of KCNQ4(G285S) and KCNQ5(G278S) with corresponding wild type KCNQ5 and KCNQ4 subunits (25,34). In the present study we also utilized a dominant-negative approach to reveal suppression of native Kv7 currents.…”

Ion channel regulation by β-secretase BACE1 – enzymatic and non-enzymatic effects beyond Alzheimer's disease

“…77,78 KCNQ4 seems to fulfil specific functions in the inner ear and in peripheral sensors, while KCNQ4/Q5 heteromers are important for vessel smooth muscle diameter control and in the vestibular system. [79][80][81] KCNQ5 has further been identified as a neuronal KCNQ member. [82][83][84] A complex molecular network is regulating the expression, localization, and gating of KCNQ channels.…”

KCNQ5 K+ channels control hippocampal synaptic inhibition and fast network oscillations

“…Hence, the altered staining pattern of Kcnq5 dn/dn hippocampi likely resulted from impaired trafficking of the mutant non-conducting protein. Instead of reaching their normal peripheral position on neurites, KCNQ5 G278S mutant channels remain in somata of pyramidal cells, similar to the recently described retention of this mutant in somata of vestibular ganglion cells 24 .…”

“…1b) further suggested that the reduced KCNQ5 labelling of st. radiatum and oriens is not owed to neurodegeneration. As KCNQ4 channels with an equivalent pore mutation (G285S) 6 show diminished plasma membrane localization in heterologous expression systems 25 and in vivo 11,24 , we rather suspected abnormal protein trafficking as the underlying cause. Indeed, when expressed in Xenopus oocytes, KCNQ5 G278S subunits carrying an extracellular HA-tag displayed reduced plasma membrane localization compared with similarly tagged wild-type (WT) KCNQ5 ( Supplementary Fig.…”

“…In the hippocampus, KCNQ5 contributes to AHP currents in the CA3 area 13 . KCNQ5 was reported to localize mainly to neuronal cell somata and dendrites in human cortex and hippocampus 21 , to glutamatergic synapses in several rat brain stem nuclei 22,23 and to the postsynaptic membrane of vestibular calyx terminals 24 . Furthermore, KCNQ5 was proposed to be located at the presynaptic membrane of the calyx of Held and to control its properties 23 .…”