Article: Polyvalent cations as permeant probes of MIC and TRPM7 pores.
2003 Volume 84, Issue 4, Page(s) 2293–2305
Abstract: ... in expressed TRPM7 and in native MIC currents, consistent with the conclusion that native MIC channels are ... cation (MIC) channel that has electrophysiological properties similar to TRPM7 Eyring rate model ... of MIC channels by polyvalent cations from the outside. ...
| Abstract | Recent studies in Jurkat T cells and in rat basophilic leukemia cells revealed an Mg(2+)-inhibited cation (MIC) channel that has electrophysiological properties similar to TRPM7 Eyring rate model expressed exogenously in mammalian cells. Here we compare the characteristics of several polyvalent cations and Mg(2+) to block monovalent MIC current from the outside. Putrescine, spermidine, spermine, PhTX-343 (a derivative of the naturally occurring polyamine toxin philanthotoxin), and Mg(2+) each blocked in a dose- and voltage-dependent manner, indicating a blocking site within the electric field of the ion channel. Spermine and the relatively bulky PhTX-343 exhibited voltage dependence steeper than that expected for the number of charges on the molecule. Polyamines and Mg(2+) are permeant blockers, as judged by relief of block at strongly negative membrane potentials. Intracellular dialysis with spermine (300 microM) had no effect, indicating an asymmetrical pore. At the single-channel level, spermine and Mg(2+) induced flickery block of 40-pS single channels. I/V characteristics and polyamine block are similar in expressed TRPM7 and in native MIC currents, consistent with the conclusion that native MIC channels are composed of TRPM7 subunits. An Eyring rate model is developed to account for I/V characteristics and block of MIC channels by polyvalent cations from the outside. |
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| MeSH term(s) | Animals ; CHO Cells/drug effects ; CHO Cells/physiology ; Calcium Channels/classification ; Calcium Channels/drug effects ; Calcium Channels/physiology ; Cation Transport Proteins/antagonists & inhibitors ; Cation Transport Proteins/classification ; Cation Transport Proteins/physiology ; Cations ; Cell Line ; Cell Line, Tumor ; Cell Membrane Permeability/drug effects ; Cricetinae ; Dose-Response Relationship, Drug ; Electric Conductivity ; Humans ; Ion Channel Gating/drug effects ; Ion Channels ; Jurkat Cells/drug effects ; Jurkat Cells/physiology ; Leukemia, Basophilic, Acute/metabolism ; Leukemia, Basophilic, Acute/physiopathology ; Magnesium/pharmacology ; Membrane Potentials/drug effects ; Membrane Proteins ; Phenols/pharmacology ; Polyamines/pharmacology ; Putrescine/pharmacology ; Rats ; Spermidine/pharmacology ; Spermine/pharmacology ; TRPM Cation Channels | ||||||||||
| Chemical Substances | Calcium Channels ; Cation Transport Proteins ; Cations ; Ion Channels ; Membrane Proteins ; Phenols ; Polyamines ; TRPM Cation Channels ; TRPM2 protein, human ; philanthotoxin 343 (115976-93-7) ; Spermine (2FZ7Y3VOQX) ; Magnesium (I38ZP9992A) ; Spermidine (U87FK77H25) ; Putrescine (V10TVZ52E4) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2003-04 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. | ||||||||||
| ZDB-ID | 218078-9 | ||||||||||
| ISSN | 1542-0086 ; 0006-3495 | ||||||||||
| ISSN (online) | 1542-0086 | ||||||||||
| ISSN | 0006-3495 | ||||||||||
| DOI | 10.1016/S0006-3495(03)75035-8 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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