| The calcium-permeable non-selective cation channel TRPM2 is modulated by cellular acidification. | |
| | |
MedLine Citation:
|
PMID: 20194125 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
TRPM2 is a calcium-permeable non-selective cation channel expressed in the plasma membrane and in lysosomes that is critically involved in aggravating reactive oxygen species (ROS)-induced inflammatory processes and has been implicated in cell death. TRPM2 is gated by ADP-ribose (ADPR) and modulated by physiological processes that produce peroxide, cyclic ADP-ribose (cADPR), nicotinamide adenine dinucleotide phosphate (NAADP) and Ca(2+). We investigated the role of extra- and intracellular acidification on heterologously expressed TRPM2 in HEK293 cells. Our results show that TRPM2 is inhibited by external acidification with an IC(50) of pH 6.5 and is completely suppressed by internal pH of 6. Current inhibition requires channel opening and is strongly voltage dependent, being most effective at negative potentials. In addition, increased cytosolic pH buffering capacity or elevated [Ca(2+)](i) reduces the rate of current inactivation elicited by extracellular acidification, and Na(+) and Ca(2+) influence the efficacy of proton-induced inactivation. Together, these results suggest that external protons permeate TRPM2 channels to gain access to an intracellular site that regulates channel activity. Consistent with this notion, single-channel measurements in HEK293 cells reveal that internal protons induce channel closure without affecting single-channel conductance, whereas external protons affect channel open probability as well as single-channel conductance of native TRPM2 in neutrophils. We conclude that protons compete with Na(+) and Ca(2+) for channel permeation and channel closure results from a competitive antagonism of protons at an intracellular Ca(2+) binding site. |
| | |
Authors:
|
John G Starkus; Andrea Fleig; Reinhold Penner |
Related Documents
:
|
10744625 - Extracellular cyclic adp-ribose increases intracellular free calcium concentration and ... 20704365 - Surface-enhanced raman spectroscopy as a tool for detecting ca2+ mobilizing second mess... 16875665 - Modulation of calcium signalling by the actin-binding protein cofilin. 1540155 - The exposure of carcinogen-initiated primary neonatal rat hepatocytes to tumor promoter... 7867805 - Involvement of mg2+ in terminating ca2+ release in cultured rat skeletal muscle. 18653675 - Control of hyperactivation in sperm. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-01 |
Journal Detail:
|
Title: The Journal of physiology Volume: 588 ISSN: 1469-7793 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 2010 Apr |
Date Detail:
|
Created Date: 2010-04-16 Completed Date: 2010-07-29 Revised Date: 2011-07-28 |
Medline Journal Info:
|
Nlm Unique ID: 0266262 Medline TA: J Physiol Country: England |
Other Details:
|
Languages: eng Pagination: 1227-40 Citation Subset: IM |
Affiliation:
|
University of Hawaii, Pacific Biosciences Research Center, Queens Medical Center, University Tower, 814, 1356 Lusitania Street, Honolulu, HI 96813, USA. johns@pbrc.hawaii.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Calcium
/
metabolism* Cell Membrane / metabolism Cell Membrane Permeability / physiology* Cells, Cultured Humans Hydrogen-Ion Concentration Kidney / cytology, metabolism* Lysosomes / metabolism Patch-Clamp Techniques TRPM Cation Channels / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
R01-GM063954/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/TRPM Cation Channels; 0/TRPM2 protein, human; 7440-70-2/Calcium |
| Comments/Corrections | |
Comment In:
|
J Physiol. 2010 May 15;588(Pt 10):1661-2
[PMID:
20472899
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: NaV1.1 channels and epilepsy.
Next Document: Vasoresponsiveness of collateral vessels in the rat hindlimb: influence of training.