KChIP1: a potential modulator to GABAergic system

Abstract

Compelling evidences from transgenic mice, immunoprecipitation data, gene expression analysis, and functional heterologous expression studies supported the role of Kv channel interacting proteins (KChIPs) as modulators of Kv4 (Shal) channels underlying the cardiac transient outward current and neuronal A-type current. Till now, there are four members (KChIP1 -4) identified in this family. KChIP1 is expressed predominantly in brain, with relative abundance in Purkinje cells of cerebellum, the reticular thalamic nuclei, the medial habenular nuclei, the hippocampus, and striatum. Our results from in situ hybridization and immunostaining assay revealed that KChIP1 was expressed in a subpopulation of parvalbumin-positive neurons suggesting its functional relationship with the GABAergic inhibitory neurons. Moreover, results obtained from KChIP1-deficient mice showed that KChIP1 mutation did not impair survival or alter the overall brain architecture, arguing against its essential function in brain development. However, the mice bearing KChIP1 deletion showed increased susceptibility to anti-GABAergic convulsive drug pentylenetetrazole-induced seizure, indicating that KChIP1 might play pivotal roles in the GABAergic inhibitory system.

The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states

“…1a,b), as high confidence protein binding partners for NEAT1. These proteins are known to reduce neuronal excitability in order to protect neurons from excessive activity1718 and were previously implicated in epileptic seizure activity1920. After validating that KCNAB2 (Fig.…”

Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxiety

“…Hot-plate and tail-flick test: KChIP1 -/- mice were generated, genotyped and breed as described[33]. In the hot-plate test, mice were placed on a standard thermal hotplate with a heated surface (55°C) (Columbus Instruments, Columbus, OH).…”

ATM-deficient human neural stem cells as an in vitro model system to study neurodegeneration

“…Concordant with this, we have observed that the amount of neurons expressing β-Tubulin III is markedly reduced in ihNSCs differentiating under hypoxia, although to the same extent in ATM-deficient and–proficient cells. Hypoxia also affects the yield of GABAergic neurons, but to a greater extent in ATM-deficient than in control ihNSCs, and the potassium channel-interacting protein-1 (KCHIP-1), predominantly expressed by GABAergic neurons [43], also appears to be markedly dependent on oxygen tension, since the fraction of positive cells falls substantially under hypoxia, and to a higher degree in ATM-deficient ihNSCs (Fig. 4A).…”

“…Loss of hypoxia-dependent inhibition of mTORC1 sensitizes ATM-deficient cells to p53-dependent apoptosis [42]. Hypoxia-induced ROS are currently believed to be the key cytosolic signal that elicits the accumulation of HIF-1α by inhibiting prolyl-hydroxylase (PHD) activity through an unknown mechanism [43]. Deregulated ROS can be neuropathological and given that ROS can activate ATM [39] to downregulate mTORC1 [44], it is possible that ATM mediates certain cellular stress responses through the hypoxia-induced ROS.…”