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Title: Kv1.3 is the exclusive voltage-gated K+ channel of platelets and megakaryocytes: roles in membrane potential, Ca2+ signalling and platelet count.
Authors: McCloskey, Conor
Jones, Sarah
Amisten, S.
Snowden, Roger T.
Kaczmarek, L. K.
Erlinge, D.
Goodall, Alison H.
Forsythe, Ian D.
Mahaut-Smith, Martyn P.
First Published: 1-May-2010
Publisher: Wiley
Citation: The Journal of Physiology, 2010, 588 (Pt 9), pp. 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 [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.
DOI Link: 10.1113/jphysiol.2010.188136
eISSN: 1469-7793
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2010 The Authors. Journal compilation © 2010 The Physiological Society. This is a Wiley OnlineOpen article, used in accordance with the terms at
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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