Document Detail

Modulation of recombinant human cardiac L-type Ca2+ channel alpha1C subunits by redox agents and hypoxia.
MedLine Citation:
PMID:  9882735     Owner:  NLM     Status:  MEDLINE    
1. Whole-cell patch clamp recordings were used to investigate the modulation by reducing and oxidizing agents of recombinant human cardiac L-type Ca2+ channel alpha1C subunits stably expressed in human embryonic kidney (HEK 293) cells. 2. The oxidizing agents thimerosal (10 microM) and p-chloromercuribenzene sulphonic acid (PCMBS; 2 microM to 2 mM) caused irreversible inhibition of Ca2+ channel currents. The reducing agent 1,4-dithiothreitol (DTT; 2 mM) was without effect on Ca2+ channel currents, but reversed the inhibitory actions of thimerosal and PCMBS. 3. Ca2+ channel currents were also inhibited by pretreatment with the methanethiosulphonate compound (2-aminoethyl)methanethiosulphonate (MTSEA, 2.5 mM), but were unaffected by identical pretreatment with (2-sulphonatoethyl)methanethiosulphonate (MTSES, 10 mM). The effects of MTSEA could be fully reversed by DTT (2 mM). The degree of current inhibition caused by 200 microM PCMBS was not significantly affected by pretreatment with MTSEA, and following PCMBS treatment, MTSEA caused a similar degree of inhibition to that observed in cells that were not previously treated with PCMBS. These findings suggested that distinct thiol groups were modulated by these two agents. 4. Hypoxic inhibition of Ca2+ channel currents was unaffected by pretreatment of cells with MTSEA but was fully prevented by treatment with PCMBS. Our results indicate that distinct cysteine residues on the alpha1C subunit can undergo redox modulation and in so doing alter channel function. Some, but not all, of these residues appear to be associated with the mechanism underlying inhibition of this channel by hypoxia.
I M Fearon; A C Palmer; A J Balmforth; S G Ball; G Varadi; C Peers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of physiology     Volume:  514 ( Pt 3)     ISSN:  0022-3751     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-26     Completed Date:  1999-03-26     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  629-37     Citation Subset:  IM    
Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, UK.
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MeSH Terms
Anoxia / metabolism*
Calcium Channel Blockers / pharmacology
Calcium Channels / chemistry,  drug effects,  metabolism*
Calcium Channels, L-Type
Cell Line
Cysteine / chemistry
Electric Stimulation
Heart / drug effects
Membrane Potentials / physiology
Myocardium / metabolism*
Oxidants / pharmacology*
Patch-Clamp Techniques
Recombinant Proteins / metabolism
Reducing Agents / pharmacology*
Grant Support
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels; 0/Calcium Channels, L-Type; 0/Oxidants; 0/Recombinant Proteins; 0/Reducing Agents; 52-90-4/Cysteine

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