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Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium

L-type Ca(2+) channels select for Ca(2+) over sodium Na(+) by an affinity-based mechanism. The prevailing model of Ca(2+) channel permeation describes a multi-ion pore that requires pore occupancy by at least two Ca(2+) ions to generate a Ca(2+) current. At [Ca(2+)] < 1 μM, Ca(2+) channels conduc...

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Autores principales: Polo-Parada, Luis, Korn, Stephen J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217043/
https://www.ncbi.nlm.nih.gov/pubmed/9222896
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author Polo-Parada, Luis
Korn, Stephen J.
author_facet Polo-Parada, Luis
Korn, Stephen J.
author_sort Polo-Parada, Luis
collection PubMed
description L-type Ca(2+) channels select for Ca(2+) over sodium Na(+) by an affinity-based mechanism. The prevailing model of Ca(2+) channel permeation describes a multi-ion pore that requires pore occupancy by at least two Ca(2+) ions to generate a Ca(2+) current. At [Ca(2+)] < 1 μM, Ca(2+) channels conduct Na(+). Due to the high affinity of the intrapore binding sites for Ca(2+) relative to Na(+), addition of μM concentrations of Ca(2+) block Na(+) conductance through the channel. There is little information, however, about the potential for interaction between Na(+) and Ca(2+) for the second binding site in a Ca(2+) channel already occupied by one Ca(2+). The two simplest possibilities, (a) that Na(+) and Ca(2+) compete for the second binding site or (b) that full time occupancy by one Ca(2+) excludes Na(+) from the pore altogether, would imply considerably different mechanisms of channel permeation. We are studying permeation mechanisms in N-type Ca(2+) channels. Similar to L-type Ca(2+) channels, N-type channels conduct Na(+) well in the absence of external Ca(2+). Addition of 10 μM Ca(2+) inhibited Na(+) conductance by 95%, and addition of 1 mM Mg(2+) inhibited Na(+) conductance by 80%. At divalent ion concentrations of 2 mM, 120 mM Na(+) blocked both Ca(2+) and Ba(2+) currents. With 2 mM Ba(2+), the IC(50) for block of Ba(2+) currents by Na(+) was 119 mM. External Li(+) also blocked Ba(2+) currents in a concentration-dependent manner, with an IC(50) of 97 mM. Na(+) block of Ba(2+) currents was dependent on [Ba(2+)]; increasing [Ba(2+)] progressively reduced block with an IC(50) of 2 mM. External Na(+) had no effect on voltage-dependent activation or inactivation of the channel. These data suggest that at physiological concentrations, Na(+) and Ca(2+) compete for occupancy in a pore already occupied by a single Ca(2+). Occupancy of the pore by Na(+) reduced Ca(2+) channel conductance, such that in physiological solutions, Ca(2+) channel currents are between 50 and 70% of maximal.
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spelling pubmed-22170432008-04-22 Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium Polo-Parada, Luis Korn, Stephen J. J Gen Physiol Article L-type Ca(2+) channels select for Ca(2+) over sodium Na(+) by an affinity-based mechanism. The prevailing model of Ca(2+) channel permeation describes a multi-ion pore that requires pore occupancy by at least two Ca(2+) ions to generate a Ca(2+) current. At [Ca(2+)] < 1 μM, Ca(2+) channels conduct Na(+). Due to the high affinity of the intrapore binding sites for Ca(2+) relative to Na(+), addition of μM concentrations of Ca(2+) block Na(+) conductance through the channel. There is little information, however, about the potential for interaction between Na(+) and Ca(2+) for the second binding site in a Ca(2+) channel already occupied by one Ca(2+). The two simplest possibilities, (a) that Na(+) and Ca(2+) compete for the second binding site or (b) that full time occupancy by one Ca(2+) excludes Na(+) from the pore altogether, would imply considerably different mechanisms of channel permeation. We are studying permeation mechanisms in N-type Ca(2+) channels. Similar to L-type Ca(2+) channels, N-type channels conduct Na(+) well in the absence of external Ca(2+). Addition of 10 μM Ca(2+) inhibited Na(+) conductance by 95%, and addition of 1 mM Mg(2+) inhibited Na(+) conductance by 80%. At divalent ion concentrations of 2 mM, 120 mM Na(+) blocked both Ca(2+) and Ba(2+) currents. With 2 mM Ba(2+), the IC(50) for block of Ba(2+) currents by Na(+) was 119 mM. External Li(+) also blocked Ba(2+) currents in a concentration-dependent manner, with an IC(50) of 97 mM. Na(+) block of Ba(2+) currents was dependent on [Ba(2+)]; increasing [Ba(2+)] progressively reduced block with an IC(50) of 2 mM. External Na(+) had no effect on voltage-dependent activation or inactivation of the channel. These data suggest that at physiological concentrations, Na(+) and Ca(2+) compete for occupancy in a pore already occupied by a single Ca(2+). Occupancy of the pore by Na(+) reduced Ca(2+) channel conductance, such that in physiological solutions, Ca(2+) channel currents are between 50 and 70% of maximal. The Rockefeller University Press 1997-06-01 /pmc/articles/PMC2217043/ /pubmed/9222896 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Polo-Parada, Luis
Korn, Stephen J.
Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium
title Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium
title_full Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium
title_fullStr Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium
title_full_unstemmed Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium
title_short Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium
title_sort block of n-type calcium channels in chick sensory neurons by external sodium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217043/
https://www.ncbi.nlm.nih.gov/pubmed/9222896
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