Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1998-4-14
|
| pubmed:abstractText |
Multiple types of high-voltage-activated Ca2+ channels, including L-, N-, P-, Q- and R-types have been distinguished from each other mainly employing pharmacological agents that selectively block particular types of Ca2+ channels. Except for the dihydropyridine-sensitive L-type Ca2+ channels, electrophysiological characterization has yet to be conducted thoroughly enough to biophysically distinguish the remaining Ca2+ channel types. In particular, the ion permeation properties of N-type Ca2+ channels have not been clarified, although the kinetic properties of both the L- and N-type Ca2+ channels are relatively well described. To establish ion conducting properties of the N-type Ca2+ channel, we examined a homogeneous population of recombinant N-type Ca2+ channels expressed in baby hamster kidney cells, using a conventional whole cell patch-clamp technique. The recombinant N-type Ca2+ channel, composed of the alpha1B, alpha2a, and beta1a subunits, displayed high-voltage-activated Ba2+ currents elicited by a test pulse more positive than -30 mV, and were strongly blocked by the N-type channel blocker omega-conotoxin-GVIA. In the presence of 110 mM Ba2+, the unitary current showed a slope conductance of 18.2 pS, characteristic of N-type channels. Ca2+ and Sr2+ resulted in smaller ion fluxes than Ba2+, with the ratio 1.0:0. 72:0.75 of maximum conductance in current-voltage relationships of Ba2+, Ca2+, and Sr2+ currents, respectively. In mixtures of Ba2+ and Ca2+, where the Ca2+ concentration was steadily increased in place of Ba2+, with the total concentration of Ba2+ and Ca2+ held constant at 3 mM, the current amplitude went through a clear minimum when 20% of the external Ba2+ was replaced by Ca+2. This anomalous mole fraction effect suggests an ion-binding site where two or more permeant ions can sit simultaneously. By using an external solution containing 110 mM Na+ without polyvalent cations, inward Na+ currents were evoked by test potentials more positive than -50 mV. These currents were activated and inactivated in a kinetic manner similar to that of Ba2+ currents. Application of inorganic Ca2+ antagonists blocked Ba2+ currents through N-type channels in a concentration-dependent manner. The rank order of inhibition was La3+ >/= Cd2+ >> Zn2+ > Ni2+ >/= Co2+. When a short strong depolarization was applied before test pulses of moderate depolarizing potentials, relief from channel blockade by La3+ and Cd2+ and subsequent channel reblocking was observed. The measured rate (2 x 10(8) M-1 s-1) of reblocking approached the diffusion-controlled limit. These results suggest that N-type Ca2+ channels share general features of a high affinity ion-binding site with the L-type Ca2+ channel, and that this site is easily accessible from the outside of the channel pore.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-Pyridinecarboxylic acid...,
http://linkedlifedata.com/resource/pubmed/chemical/Barium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Cations, Divalent,
http://linkedlifedata.com/resource/pubmed/chemical/Nimodipine,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Spider Venoms,
http://linkedlifedata.com/resource/pubmed/chemical/Strontium,
http://linkedlifedata.com/resource/pubmed/chemical/omega-Agatoxin IVA,
http://linkedlifedata.com/resource/pubmed/chemical/omega-Conotoxin GVIA
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
|
| pubmed:issn |
0022-3077
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
79
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
622-34
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:9463426-3-Pyridinecarboxylic acid...,
pubmed-meshheading:9463426-Action Potentials,
pubmed-meshheading:9463426-Animals,
pubmed-meshheading:9463426-Barium,
pubmed-meshheading:9463426-Binding Sites,
pubmed-meshheading:9463426-Calcium,
pubmed-meshheading:9463426-Calcium Channel Blockers,
pubmed-meshheading:9463426-Calcium Channels,
pubmed-meshheading:9463426-Cations, Divalent,
pubmed-meshheading:9463426-Cell Line,
pubmed-meshheading:9463426-Cricetinae,
pubmed-meshheading:9463426-Ion Channel Gating,
pubmed-meshheading:9463426-Ion Transport,
pubmed-meshheading:9463426-Kidney,
pubmed-meshheading:9463426-Kinetics,
pubmed-meshheading:9463426-Mesocricetus,
pubmed-meshheading:9463426-Nimodipine,
pubmed-meshheading:9463426-Patch-Clamp Techniques,
pubmed-meshheading:9463426-Peptides,
pubmed-meshheading:9463426-Rabbits,
pubmed-meshheading:9463426-Recombinant Fusion Proteins,
pubmed-meshheading:9463426-Spider Venoms,
pubmed-meshheading:9463426-Strontium,
pubmed-meshheading:9463426-Transfection,
pubmed-meshheading:9463426-omega-Agatoxin IVA,
pubmed-meshheading:9463426-omega-Conotoxin GVIA
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| pubmed:year |
1998
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| pubmed:articleTitle |
Functional characterization of ion permeation pathway in the N-type Ca2+ channel.
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| pubmed:affiliation |
Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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