NDLI: Inactivation of TRPM2 Channels by Extracellular Divalent Copper

Content Provider	PubMed Central
Author	Yu, Wenyue Jiang, Lin-hua Zheng, Yang Hu, Xupang Luo, Jianhong Yang, Wei
Editor	Xu, Shang-zhong
Copyright Year	2014
Abstract	Cu2+ is an essential metal ion that plays a critical role in the regulation of a number of ion channels and receptors in addition to acting as a cofactor in a variety of enzymes. Here, we showed that human melastatin transient receptor potential 2 (hTRPM2) channel is sensitive to inhibition by extracellular Cu2+. Cu2+ at concentrations as low as 3 µM inhibited the hTRPM2 channel completely and irreversibly upon washing or using Cu2+ chelators, suggesting channel inactivation. The Cu2+-induced inactivation was similar when the channels conducted inward or outward currents, indicating the permeating ions had little effect on Cu2+-induced inactivation. Furthermore, Cu2+ had no effect on singe channel conductance. Alanine substitution by site-directed mutagenesis of His995 in the pore-forming region strongly attenuated Cu2+-induced channel inactivation, and mutation of several other pore residues to alanine altered the kinetics of channel inactivation by Cu2+. In addition, while introduction of the P1018L mutation is known to result in channel inactivation, exposure to Cu2+ accelerated the inactivation of this mutant channel. In contrast with the hTRPM2, the mouse TRPM2 (mTRPM2) channel, which contains glutamine at the position equivalent to His995, was insensitive to Cu2+. Replacement of His995 with glutamine in the hTRPM2 conferred loss of Cu2+-induced channel inactivation. Taken together, these results suggest that Cu2+ inactivates the hTRPM2 channel by interacting with the outer pore region. Our results also indicate that the amino acid residue difference in this region gives rise to species-dependent effect by Cu2+ on the human and mouse TRPM2 channels.
Related Links	http://dx.doi.org/10.1371/journal.pone.0112071
Starting Page	112071
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

TRPM2 Cation Channels Modulate T Cell Effector Functions and Contribute to Autoimmune CNS Inflammation

A Kir6.2 Pore Mutation Causes Inactivation of ATP-Sensitive Potassium Channels by Disrupting PIP2-Dependent Gating

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation

Lysine-Rich Extracellular Rings Formed by hβ2 Subunits Confer the Outward Rectification of BK Channels

The Eag Domain Regulates the Voltage-Dependent Inactivation of Rat Eag1 K+ Channels

Role of TRPM2 in H2O2-Induced Cell Apoptosis in Endothelial Cells

Conserved N-Terminal Negative Charges Support Optimally Efficient N-type Inactivation of Kv1 Channels

A Cell Permeable NPE Caged ADP-Ribose for Studying TRPM2

Transcriptome of Extracellular Vesicles Released by Hepatocytes

Inactivation of TRPM2 Channels by Extracellular Divalent Copper

Similar Documents

TRPM2 Cation Channels Modulate T Cell Effector Functions and Contribute to Autoimmune CNS Inflammation

A Kir6.2 Pore Mutation Causes Inactivation of ATP-Sensitive Potassium Channels by Disrupting PIP2-Dependent Gating

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation

Lysine-Rich Extracellular Rings Formed by hβ2 Subunits Confer the Outward Rectification of BK Channels

The Eag Domain Regulates the Voltage-Dependent Inactivation of Rat Eag1 K+ Channels

Role of TRPM2 in H2O2-Induced Cell Apoptosis in Endothelial Cells

Conserved N-Terminal Negative Charges Support Optimally Efficient N-type Inactivation of Kv1 Channels

A Cell Permeable NPE Caged ADP-Ribose for Studying TRPM2

Transcriptome of Extracellular Vesicles Released by Hepatocytes

Inactivation of TRPM2 Channels by Extracellular Divalent Copper