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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 ; 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
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
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
2010-06-22 09:39:19
date last changed
2018-05-29 11:40:49
@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},
  volume       = {588},
  year         = {2010},
}