Source:http://linkedlifedata.com/resource/pubmed/id/19562244
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2009-8-27
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pubmed:abstractText |
We have previously shown that the membrane conductance of mIMCD-3 cells at a holding potential of 0 mV is dominated by a Ca2+-dependent Cl(-) current (I(CLCA)). Here we report that I(CLCA) activity is also voltage dependent and that this dependence on voltage is linked to the opening of a novel Al3+-sensitive, voltage-dependent, Ca2+ influx pathway. Using whole-cell patch-clamp recordings at a physiological holding potential (-60 mV), ICLCA was found to be inactive and resting currents were predominantly K+ selective. However, membrane depolarization to 0 mV resulted in a slow, sigmoidal, activation of ICLCA (T(0.5) approximately 500 s), while repolarization in turn resulted in a monoexponential decay in I(CLCA) (T (0.5) approximately 100 s). The activation of I(CLCA) by depolarization was reduced by lowering extracellular Ca2+ and completely inhibited by buffering cytosolic Ca2+ with EGTA, suggesting a role for Ca2+ influx in the activation of I(CLCA). However, raising bulk cytosolic Ca2+ at -60 mV did not produce sustained I(CLCA) activity. Therefore I(CLCA) is dependent on both an increase in intracellular Ca2+ and depolarization to be active. We further show that membrane depolarization is coupled to opening of a Ca2+ influx pathway that displays equal permeability to Ca2+ and Ba2+ ions and that is blocked by extracellular Al3+ and La3+. Furthermore, Al3+ completely and reversibly inhibited depolarization-induced activation of ICLCA, thereby directly linking Ca2+ influx to activation of I(CLCA). We speculate that during sustained membrane depolarization, calcium influx activates ICLCA which functions to modulate NaCl transport across the apical membrane of IMCD cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1432-1424
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
230
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
57-68
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pubmed:meshHeading |
pubmed-meshheading:19562244-Animals,
pubmed-meshheading:19562244-Calcium,
pubmed-meshheading:19562244-Calcium Signaling,
pubmed-meshheading:19562244-Cell Line,
pubmed-meshheading:19562244-Chloride Channels,
pubmed-meshheading:19562244-Chlorine,
pubmed-meshheading:19562244-Electric Conductivity,
pubmed-meshheading:19562244-Ion Channel Gating,
pubmed-meshheading:19562244-Kidney Tubules, Collecting,
pubmed-meshheading:19562244-Membrane Potentials,
pubmed-meshheading:19562244-Mice
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pubmed:year |
2009
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pubmed:articleTitle |
A voltage-dependent Ca2+ influx pathway regulates the Ca2+-dependent Cl(-) conductance of renal IMCD-3 cells.
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pubmed:affiliation |
Epithelial Research Group, Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne NE2-4HH, UK.
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pubmed:publicationType |
Journal Article
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