Kv1.3 is the exclusive voltage-gated K+ channel of platelets and megakaryocytes_ roles in membrane potential, Ca2+ signalling and platelet count..pdf (368.21 kB)

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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journal contribution
posted on 24.10.2012, 09:03 by Conor McCloskey, Sarah Jones, S. Amisten, Roger T. Snowden, L. K. Kaczmarek, D. Erlinge, Alison H. Goodall, Ian D. Forsythe, Martyn P. Mahaut-Smith
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.

History

Citation

The Journal of Physiology, 2010, 588 (Pt 9), pp. 1399-1406

Version

VoR (Version of Record)

Published in

The Journal of Physiology

Publisher

Wiley

eissn

1469-7793

Copyright date

2010

Available date

24/10/2012

Publisher version

http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2010.188136/abstract

Language

eng

Exports