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Kv1.3 is the exclusive voltage-gated K+ channel of platelets and megakaryocytes : roles in membrane potential, Ca2+ signalling and platelet count
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McCloskey, Conor, Jones, Sarah, Amisten, Stefan, Snowden, Roger T., Kaczmarek, Leonard K., Erlinge, David, Goodall, Alison H., Forsythe, Ian D. and Mahaut-Smith, Martyn P.. (2010) Kv1.3 is the exclusive voltage-gated K+ channel of platelets and megakaryocytes : roles in membrane potential, Ca2+ signalling and platelet count. Journal of Physiology, Vol.588 (No.9). pp. 1399-1406. ISSN 0022-3751
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Official URL: http://dx.doi.org/10.1113/jphysiol.2010.188136
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 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 P2X1- and thromboxaneA2 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.
| Item Type: | Journal Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Warwick Medical School > Reproductive Health Faculty of Medicine > Warwick Medical School |
| Journal or Publication Title: | Journal of Physiology |
| Publisher: | Wiley-Blackwell Publishing Ltd. |
| ISSN: | 0022-3751 |
| Date: | 1 May 2010 |
| Volume: | Vol.588 |
| Number: | No.9 |
| Page Range: | pp. 1399-1406 |
| Identification Number: | 10.1113/jphysiol.2010.188136 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| URI: | http://wrap.warwick.ac.uk/id/eprint/45944 |
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