Distribution of M-channel subunits KCNQ2 and KCNQ3 in rat hippocampus

Abstract

Neuronal M-channels are low threshold, slowly activating and non-inactivating, voltage dependent K+ channels that play a crucial role in controlling neuronal excitability. The native M-channel is composed of heteromeric or homomeric assemblies of subunits belonging to the Kv7/KCNQ family, with KCNQ2/3 heteromers being the most abundant form. KCNQ2 and KCNQ3 subunits have been found to be expressed in various neurons in the central and peripheral nervous system of rodents and humans. Previous evidence shows preferential localization of both subunits to axon initial segments, somata and nodes of Ranvier. In this work, we show the distribution and co-localization of KCNQ2 and KCNQ3 subunits throughout the hippocampal formation, via immunostaining experiments on unfixed rat brain slices and confocal microscopy. We find intense localization and colocalization to the axonal initial segment in several regions of the hippocampus, as well as staining for non-neuronal cells in the area of the lateral ventricle. We did not observe colocalization of KCNQ2 or KCNQ3 with the presynaptic protein, synaptophysin.

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

“…6a-c). As described previously 12,13,32 , we rather detected these channels at axon initial segments and nodes of Ranvier ( Supplementary Fig. 6d).…”

“…Importantly, our 'dominant-negative' strategy, in which all heteromeric channels containing one or more KCNQ5 subunit(s) are inactivated, avoided the possibility of the formation of more efficient KCNQ2/3 heteromers that may occur in Kcnq5 À / À mice. KCNQ2, -3 and -5 are broadly expressed in the brain and show robust expression in the hippocampus 13,19,32,33 . All three isoforms, as well as KCNQ2/3 and KCNQ3/5 heteromers, mediate K þ currents that slowly activate upon membrane depolarization.…”

Effects of Estrogen on Neuronal KCNQ2/3 Channels Expressed in PC-12 Cells

“…Results from immunohistochemistry study have shown that KCNQ2/3 channels are localized to the axon initial segment (AIS) in hippocampus. 19) Electrophysiological recordings have demonstrated the functional involvement of KCNQ2/3 channels in hippocampal plasticity. Application or injection of KCNQ2/KCNQ3 channel blockers lowered the threshold for LTP induction 20,21) and reversed the cognitive impairment in animal models of cognitive disease.…”

Regulation of neuronal KCNQ2 channel by Src: dual rearrangement of cytosolic termini underlies bidirectional gating regulation

“…M-channels are members of the Kv7 family of voltage-dependent K + channels and are expressed predominantly in neuronal cells, with the most abundant subunits being KCNQ2 (Q2) and KCNQ3 (Q3) (Brown and Adams, 1980;Wang et al, 1998;Jentsch, 2000;Robbins, 2001;Klinger et al, 2011). Although heteromeric Q2-Q3 channels are expressed in the cell bodies and dendrites of many hippocampal and cortical neurons (Marrion, 1997;Cooper and Jan, 2003) and also in the initial segment of several neurons (Devaux et al, 2004;Chung et al, 2006;Klinger et al, 2011), where they control neuronal excitability by limiting repetitive firing (Hille, 1992;Dolly and Parcej, 1996;Miller, 2000;Millar et al, 2007;Regev et al, 2009), exclusive expression of Q2 subunits can be found in nerve terminals, where homomeric Q2 channels might directly regulate neurotransmitter release (Cooper and Jan, 2003;Devaux et al, 2004;Martire et al, 2004;Peretz et al, 2007).…”

“…Although heteromeric Q2-Q3 channels are expressed in the cell bodies and dendrites of many hippocampal and cortical neurons (Marrion, 1997;Cooper and Jan, 2003) and also in the initial segment of several neurons (Devaux et al, 2004;Chung et al, 2006;Klinger et al, 2011), where they control neuronal excitability by limiting repetitive firing (Hille, 1992;Dolly and Parcej, 1996;Miller, 2000;Millar et al, 2007;Regev et al, 2009), exclusive expression of Q2 subunits can be found in nerve terminals, where homomeric Q2 channels might directly regulate neurotransmitter release (Cooper and Jan, 2003;Devaux et al, 2004;Martire et al, 2004;Peretz et al, 2007). In humans, mutations in KCNQ2 are associated with benign (BFNC; Biervert et al, 1998;Singh et al, 1998) and non-benign (encephalopathy; Weckhuysen et al, 2012) neonatal forms of epilepsy.…”