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Kv1.3 is the exclusive voltage-gated K plus channel of platelets and megakaryocytes: roles in membrane potential, Ca2+signalling and platelet count

McCloskey, Conor ; Jones, Sarah ; Amisten, Stefan ; Snowden, Roger T. ; Kaczmarek, Leonard K. ; Erlinge, David LU orcid ; Goodall, Alison H. ; Forsythe, Ian D. and Mahaut-Smith, Martyn P. (2010) In Journal of Physiology 588(9). p.1399-1406
Abstract
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 alpha 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 [Ca2+](i) increases and delayed the onset of store-operated Ca2+ influx. Megakaryocyte development was normal in Kv1.3-/- mice, but the platelet... (More)
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 alpha 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 [Ca2+](i) increases and delayed the onset of store-operated Ca2+ 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 Ca2+ increases and influences circulating platelet numbers. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physiology
volume
588
issue
9
pages
1399 - 1406
publisher
The Physiological Society
external identifiers
  • wos:000277208000010
  • scopus:77952931363
  • pmid:20308249
ISSN
1469-7793
DOI
10.1113/jphysiol.2010.188136
language
English
LU publication?
yes
id
484b8ad4-a78e-498b-81b8-0df81b7d5327 (old id 1619359)
date added to LUP
2016-04-01 13:05:06
date last changed
2025-10-14 13:12:35
@article{484b8ad4-a78e-498b-81b8-0df81b7d5327,
  abstract     = {{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 alpha 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 [Ca2+](i) increases and delayed the onset of store-operated Ca2+ 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 Ca2+ increases and influences circulating platelet numbers.}},
  author       = {{McCloskey, Conor and Jones, Sarah and Amisten, Stefan and Snowden, Roger T. and Kaczmarek, Leonard K. and Erlinge, David and Goodall, Alison H. and Forsythe, Ian D. and Mahaut-Smith, Martyn P.}},
  issn         = {{1469-7793}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1399--1406}},
  publisher    = {{The Physiological Society}},
  series       = {{Journal of Physiology}},
  title        = {{Kv1.3 is the exclusive voltage-gated K plus channel of platelets and megakaryocytes: roles in membrane potential, Ca2+signalling and platelet count}},
  url          = {{http://dx.doi.org/10.1113/jphysiol.2010.188136}},
  doi          = {{10.1113/jphysiol.2010.188136}},
  volume       = {{588}},
  year         = {{2010}},
}