Kv1.3 is the exclusive voltage-gated K plus channel of platelets and megakaryocytes: roles in membrane potential, Ca2+signalling and platelet count
(2010) In Journal of Physiology 588(9). p.1399-1406- 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 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1619359
- author
- McCloskey, Conor ; Jones, Sarah ; Amisten, Stefan ; Snowden, Roger T. ; Kaczmarek, Leonard K. ; Erlinge, David LU ; Goodall, Alison H. ; Forsythe, Ian D. and Mahaut-Smith, Martyn P.
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Physiology
- volume
- 588
- issue
- 9
- pages
- 1399 - 1406
- publisher
- The Physiological Society
- external identifiers
-
- wos:000277208000010
- scopus:77952931363
- pmid:20308249
- ISSN
- 1469-7793
- DOI
- 10.1113/jphysiol.2010.188136
- language
- English
- LU publication?
- yes
- id
- 484b8ad4-a78e-498b-81b8-0df81b7d5327 (old id 1619359)
- date added to LUP
- 2016-04-01 13:05:06
- date last changed
- 2022-04-13 23:07:36
@article{484b8ad4-a78e-498b-81b8-0df81b7d5327, 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 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.}}, author = {{McCloskey, Conor and Jones, Sarah and Amisten, Stefan and Snowden, Roger T. and Kaczmarek, Leonard K. and Erlinge, David and Goodall, Alison H. and Forsythe, Ian D. and Mahaut-Smith, Martyn P.}}, issn = {{1469-7793}}, language = {{eng}}, number = {{9}}, pages = {{1399--1406}}, publisher = {{The Physiological Society}}, series = {{Journal of Physiology}}, title = {{Kv1.3 is the exclusive voltage-gated K plus channel of platelets and megakaryocytes: roles in membrane potential, Ca2+signalling and platelet count}}, url = {{http://dx.doi.org/10.1113/jphysiol.2010.188136}}, doi = {{10.1113/jphysiol.2010.188136}}, volume = {{588}}, year = {{2010}}, }