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J Physiol Volume 576, Number 1, 151-162, October 1, 2006 DOI: 10.1113/jphysiol.2006.113886
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CELLULAR

Molecular and electrophysiological characterization of transient receptor potential ion channels in the primary murine megakaryocyte

Richard N. Carter1, Gwen Tolhurst1, Gemma Walmsley1, Matthieu Vizuete-Forster1, Nigel Miller2 and Martyn P. Mahaut-Smith1

1 Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
2 Department of Pathology, University of Cambridge, Cambridge, UK

The molecular identity of platelet Ca2+ entry pathways is controversial. Furthermore, the extent to which Ca2+-permeable ion channels are functional in these tiny, anucleate cells is difficult to assess by direct electrophysiological measurements. Recent work has highlighted how the primary megakaryocyte represents a bona fide surrogate for studies of platelet signalling, including patch clamp recordings of ionic conductances. We have now screened for all known members of the transient receptor potential (TRP) family of non-selective cation channels in murine megakaryocytes following individual selection of these rare marrow cells using glass micropipettes. RT-PCR detected messages for TRPC6 and TRPC1, which have been reported in platelets and megakaryocytic cell lines, and TRPM1, TRPM2 and TRPM7, which to date have not been demonstrated in cells of megakaryocytic/platelet lineage. Electrophysiological recordings demonstrated the presence of functional TRPM7, a constitutively active cation channel sensitive to intracellular Mg2+, and TRPM2, an ADP-ribose-dependent cation channel activated by oxidative stress. In addition, the electrophysiological and pharmacological properties of the non-selective cation channels stimulated by the physiological agonist ADP are consistent with a major role for TRPC6 in this G-protein-coupled receptor-dependent Ca2+ influx pathway. This study defines for the first time the principal TRP channels within the primary megakaryocyte, which represent candidates for Ca2+ influx pathways activated by a diverse range of stimuli in the platelet and megakaryocyte.

(Received 22 May 2006; accepted after revision 14 July 2006; first published online 20 July 2006)
Corresponding author M. P. Mahaut-Smith: Department of Physiology, Development and Neuroscience, Physiology Building, University of Cambridge, Downing Street, Cambridge, CB2 3EG UK. Email: mpm11{at}cam.ac.uk

R. N. Carter and G. Tolhurst contributed equally to this study and should be considered joint first authors.






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