McCloskey, Conor Jones, Sarah Amisten, S. Snowden, Roger T. Kaczmarek, L. K. Erlinge, D. Goodall, Alison H. Forsythe, Ian D. Mahaut-Smith, Martyn P. Kv1.3 is the exclusive voltage-gated K+ channel of platelets and megakaryocytes: roles in membrane potential, Ca2+ signalling and platelet count. 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. Animals;Blood Platelets;Calcium Signaling;Cell Size;DNA;Complementary;Humans;Kv1.3 Potassium Channel;Megakaryocytes;Membrane Potentials;Mice;Inbred C57BL;Patch-Clamp Techniques;Platelet Count;Reverse Transcriptase Polymerase Chain Reaction;Scorpion Venoms;Second Messenger Systems 2012-10-24
    https://figshare.le.ac.uk/articles/journal_contribution/Kv1_3_is_the_exclusive_voltage-gated_K_channel_of_platelets_and_megakaryocytes_roles_in_membrane_potential_Ca2_signalling_and_platelet_count_/10113410