TY - JOUR
T1 - Kv1.3 is the exclusive voltage-gated K+ channel of platelets and megakaryocytes: Roles in membrane potential, Ca2+ signalling and platelet count
AU - McCloskey, Conor
AU - Jones, Sarah
AU - Amisten, Stefan
AU - Snowden, Roger T.
AU - Kaczmarek, Leonard K.
AU - Erlinge, David
AU - Goodall, Alison H.
AU - Forsythe, Ian D.
AU - Mahaut-Smith, Martyn P.
N1 - McCloskey, Conor Jones, Sarah Amisten, Stefan Snowden, Roger T Kaczmarek, Leonard K Erlinge, David Goodall, Alison H Forsythe, Ian D Mahaut-Smith, Martyn P 05/014/Biotechnology and Biological Sciences Research Council/United Kingdom PG06/028/British Heart Foundation/United Kingdom Medical Research Council/United Kingdom In Vitro Research Support, Non-U.S. Gov't England The Journal of physiology J Physiol. 2010 May 1;588(Pt 9):1399-406. Epub 2010 Mar 22.
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Animals
KW - Blood Platelets/drug effects/physiology/ultrastructure
KW - Calcium Signaling/drug effects/physiology
KW - Cell Size
KW - DNA, Complementary/biosynthesis/genetics
KW - Humans
KW - Kv1.3 Potassium Channel/blood
KW - Megakaryocytes/drug effects/physiology/ultrastructure
KW - Membrane Potentials/drug effects/physiology
KW - Mice
KW - Mice, Inbred C57BL
KW - Patch-Clamp Techniques
KW - Platelet Count
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Scorpion Venoms/pharmacology
KW - Second Messenger Systems/physiology
U2 - 10.1113/jphysiol.2010.188136
DO - 10.1113/jphysiol.2010.188136
M3 - Article
SN - 0022-3751
VL - 588
SP - 1399
EP - 1406
JO - Journal of Physiology
JF - Journal of Physiology
IS - 9
ER -