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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...

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Autores principales: McCloskey, Conor, Jones, Sarah, Amisten, Stefan, Snowden, Roger T, Kaczmarek, Leonard K, Erlinge, David, Goodall, Alison H, Forsythe, Ian D, Mahaut-Smith, Martyn P
Formato: Texto
Lenguaje:English
Publicado: Blackwell Science Inc 2010
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.
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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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