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

Conor McCloskey, Sarah Jones, Stefan Amisten, Roger T. Snowden, Leonard K. Kaczmarek, David Erlinge, Alison H. Goodall, Ian D. Forsythe, Martyn P. Mahaut-Smith

    Research output: Contribution to journalArticlepeer-review

    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. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.
    Original languageEnglish
    Pages (from-to)1399-1406
    Number of pages7
    JournalJournal of Physiology
    Volume588
    Issue number9
    DOIs
    Publication statusPublished - May 2010

    Keywords

    • Animals
    • Blood Platelets/drug effects/*physiology/ultrastructure
    • Calcium Signaling/drug effects/*physiology
    • Cell Size
    • DNA, Complementary/biosynthesis/genetics
    • Humans
    • Kv1.3 Potassium Channel/*blood
    • Megakaryocytes/drug effects/*physiology/ultrastructure
    • Membrane Potentials/drug effects/*physiology
    • Mice
    • Mice, Inbred C57BL
    • Patch-Clamp Techniques
    • *Platelet Count
    • Reverse Transcriptase Polymerase Chain Reaction
    • Scorpion Venoms/pharmacology
    • Second Messenger Systems/physiology

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