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Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count
A delayed rectifier voltage-gated K(+) channel (Kv) represents the largest ionic conductance of platelets and megakaryocytes, but is undefined at the molecular level. Quantitative RT-PCR of all known Kv α and ancillary subunits showed that only Kv1.3 (KCNA3) is substantially expressed in human plate...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Blackwell Science Inc
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876798/ https://www.ncbi.nlm.nih.gov/pubmed/20308249 http://dx.doi.org/10.1113/jphysiol.2010.188136 |
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author | McCloskey, Conor Jones, Sarah Amisten, Stefan Snowden, Roger T Kaczmarek, Leonard K Erlinge, David Goodall, Alison H Forsythe, Ian D Mahaut-Smith, Martyn P |
author_facet | McCloskey, Conor Jones, Sarah Amisten, Stefan Snowden, Roger T Kaczmarek, Leonard K Erlinge, David Goodall, Alison H Forsythe, Ian D Mahaut-Smith, Martyn P |
author_sort | McCloskey, Conor |
collection | PubMed |
description | A delayed rectifier voltage-gated K(+) channel (Kv) represents the largest ionic conductance of platelets and megakaryocytes, but is undefined at the molecular level. Quantitative RT-PCR of all known Kv α and ancillary subunits showed that only Kv1.3 (KCNA3) is substantially expressed in human platelets. Furthermore, megakaryocytes from Kv1.3(−/−) mice or from wild-type mice exposed to the Kv1.3 blocker margatoxin completely lacked Kv currents and displayed substantially depolarised resting membrane potentials. In human platelets, margatoxin reduced the P2X(1)- and thromboxaneA(2) receptor-evoked [Ca(2+)](i) increases and delayed the onset of store-operated Ca(2+) influx. Megakaryocyte development was normal in Kv1.3(−/−) mice, but the platelet count was increased, consistent with a role of Kv1.3 in apoptosis or decreased platelet activation. We conclude that Kv1.3 forms the Kv channel of the platelet and megakaryocyte, which sets the resting membrane potential, regulates agonist-evoked Ca(2+) increases and influences circulating platelet numbers. |
format | Text |
id | pubmed-2876798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Blackwell Science Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-28767982010-12-31 Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count McCloskey, Conor Jones, Sarah Amisten, Stefan Snowden, Roger T Kaczmarek, Leonard K Erlinge, David Goodall, Alison H Forsythe, Ian D Mahaut-Smith, Martyn P J Physiol Molecular and Cellular A delayed rectifier voltage-gated K(+) channel (Kv) represents the largest ionic conductance of platelets and megakaryocytes, but is undefined at the molecular level. Quantitative RT-PCR of all known Kv α and ancillary subunits showed that only Kv1.3 (KCNA3) is substantially expressed in human platelets. Furthermore, megakaryocytes from Kv1.3(−/−) mice or from wild-type mice exposed to the Kv1.3 blocker margatoxin completely lacked Kv currents and displayed substantially depolarised resting membrane potentials. In human platelets, margatoxin reduced the P2X(1)- and thromboxaneA(2) receptor-evoked [Ca(2+)](i) increases and delayed the onset of store-operated Ca(2+) influx. Megakaryocyte development was normal in Kv1.3(−/−) mice, but the platelet count was increased, consistent with a role of Kv1.3 in apoptosis or decreased platelet activation. We conclude that Kv1.3 forms the Kv channel of the platelet and megakaryocyte, which sets the resting membrane potential, regulates agonist-evoked Ca(2+) increases and influences circulating platelet numbers. Blackwell Science Inc 2010-05-01 2010-03-22 /pmc/articles/PMC2876798/ /pubmed/20308249 http://dx.doi.org/10.1113/jphysiol.2010.188136 Text en Journal compilation © 2010 The Physiological Society |
spellingShingle | Molecular and Cellular McCloskey, Conor Jones, Sarah Amisten, Stefan Snowden, Roger T Kaczmarek, Leonard K Erlinge, David Goodall, Alison H Forsythe, Ian D Mahaut-Smith, Martyn P Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count |
title | Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count |
title_full | Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count |
title_fullStr | Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count |
title_full_unstemmed | Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count |
title_short | Kv1.3 is the exclusive voltage-gated K(+) channel of platelets and megakaryocytes: roles in membrane potential, Ca(2+) signalling and platelet count |
title_sort | kv1.3 is the exclusive voltage-gated k(+) channel of platelets and megakaryocytes: roles in membrane potential, ca(2+) signalling and platelet count |
topic | Molecular and Cellular |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876798/ https://www.ncbi.nlm.nih.gov/pubmed/20308249 http://dx.doi.org/10.1113/jphysiol.2010.188136 |
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