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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 (author)
- Jones, Sarah (author)
- Amisten, Stefan (author)
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- Snowden, Roger T. (author)
- Kaczmarek, Leonard K. (author)
- Goodall, Alison H. (author)
- Forsythe, Ian D. (author)
- Mahaut-Smith, Martyn P. (author)
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- (creator_code:org_t)
- 2010-04-30
- 2010
- English.
- In: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 588:9, s. 1399-1406
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
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- MEDICAL AND HEALTH SCIENCES
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- Lund University
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