KChIP1: a potential modulator to GABAergic system.
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.
Xiong
Hui
H
School of Life Sciences, Fudan University, Shanghai 200433, China.
Xia
Kun
K
Li
Benshang
B
Zhao
Guoping
G
Zhang
Zhuohua
Z
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D005260:Female; D018756:GABA Antagonists; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051605:Kv Channel-Interacting Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D010433:Pentylenetetrazole; D018079:Receptors, GABA / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced / Q000235:genetics
D018756:GABA Antagonists; C496754:Kcnip1 protein, mouse; D051605:Kv Channel-Interacting Proteins; D010320:Parvalbumins; D018079:Receptors, GABA; D010433:Pentylenetetrazole