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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1997-6-12
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pubmed:abstractText |
The gating of ryanodine receptor calcium release channels (RyRs) depends on myoplasmic Ca2+ and Mg2+ concentrations. RyRs from skeletal and cardiac muscle are activated by microm Ca2+ and inhibited by mm Ca2+ and Mg2+. 45Ca2+ release from skeletal SR vesicles suggests two mechanisms for Mg2+-inhibition (Meissner, Darling & Eveleth, 1986, Biochemistry 25:236-244). The present study investigates the nature of these mechanisms using measurements of single-channel activity from cardiac- and skeletal RyRs incorporated into planar lipid bilayers. Our measurements of Mg2+- and Ca2+-dependent gating kinetics confirm that there are two mechanisms for Mg2+ inhibition (Type I and II inhibition) in skeletal and cardiac RyRs. The mechanisms operate concurrently, are independent and are associated with different parts of the channel protein. Mg2+ reduces Po by competing with Ca2+ for the activation site (Type-I) or binding to more than one, and probably two low affinity inhibition sites which do not discriminate between Ca2+ and Mg2+ (Type-II). The relative contributions of the two inhibition mechanisms to the total Mg2+ effect depend on cytoplasmic [Ca2+] in such a way that Mg2+ inhibition has the properties of Types-I and II inhibition at low and high [Ca2+] respectively. Both mechanisms are equally important when [Ca2+] = 10 microm in cardiac RyRs or 1 microm in skeletal RyRs. We show that Type-I inhibition is not the sole mechanism responsible for Mg2+ inhibition, as is often assumed, and we discuss the physiological implications of this finding.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Magnesium,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine Receptor Calcium Release...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-2631
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
156
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
213-29
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9096063-Animals,
pubmed-meshheading:9096063-Calcium,
pubmed-meshheading:9096063-Calcium Channels,
pubmed-meshheading:9096063-Ion Channel Gating,
pubmed-meshheading:9096063-Ion Transport,
pubmed-meshheading:9096063-Kinetics,
pubmed-meshheading:9096063-Magnesium,
pubmed-meshheading:9096063-Models, Biological,
pubmed-meshheading:9096063-Muscle, Skeletal,
pubmed-meshheading:9096063-Muscle Proteins,
pubmed-meshheading:9096063-Myocardium,
pubmed-meshheading:9096063-Ryanodine Receptor Calcium Release Channel,
pubmed-meshheading:9096063-Sarcoplasmic Reticulum
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pubmed:year |
1997
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pubmed:articleTitle |
Magnesium inhibition of ryanodine-receptor calcium channels: evidence for two independent mechanisms.
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pubmed:affiliation |
Muscle Research Group, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT 2601, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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