Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands

Content Provider	Semantic Scholar
Author	Kinoshita, Maho Matsuoka, Yoshikazu Suzuki, Takeshi Mirrielees, Jennifer A. Yang, Jay
Copyright Year	2012
Abstract	Sigma1 receptors (Sigma1R) are intracellular chaperone proteins that bind psychotropic drugs and also clinically used drugs such as ketamine and haloperidol. Co-expression of the Sigma1R has been reported to enhance the sensitivity of several voltage-gated ion channels to Sigma1R ligands. Kv1.3 is the predominant voltage-gated potassium channel expressed in T lymphocytes with a documented role in immune activation. To gain a better understanding of Sigma1R modulation of Kv ion channels, we investigated the effects of Sigma1R co-expression on Kv1.3 physiology and pharmacology in ion channels expressed in Xenopus oocytes. We also explored the protein domains of Kv1.3 necessary for protein:protein interaction between Kv1.3 and Sigma1R through co-immunoprecipitation studies. Slowly inactivating outward-going currents consistent with Kv1.3 expression were elicited on step depolarizations. The current characterized by E(rev), V(1/2), and slope factor remained unchanged when co-expressed with Sigma1R. Analysis of inactivation time constant revealed a faster Kv1.3 current decay when co-expressed with Sigma1R. However the sensitivity to Sigma1R ligands remained unaltered when co-expressed with the Sigma1R in contrast to the previously reported modulation of ligand sensitivity in closely related Kv1.4 and Kv1.5 voltage gated potassium channels. Co-immunoprecipitation assays of various Kv1.3 truncation constructs indicated that the transmembrane domain of the Kv1.3 protein was responsible for the protein:protein interaction with the Sigma1R. Sigma1R likely interacts with different domains of Kv ion channel family proteins resulting in distinct modulation of different channels.
Starting Page	1
Ending Page	9
Page Count	9
File Format	PDF HTM / HTML
DOI	10.1016/j.brainres.2012.02.070
PubMed reference number	22433979
Journal	Medline
Volume Number	1452
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S0006899312004325
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S0006899312004325?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/j.brainres.2012.02.070
Journal	Brain Research
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article