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

• DOI: 10.1113/jphysiol.2006.113886
• Publication Date: 2006-07-21T00:24:43Z
• Authors: Richard N. Carter; Gwen Tolhurst; Gemma Walmsley; Matthieu Vizuete‐...; Nigel Miller; Martyn P. Mahaut‐...
• Keywords: TRPM2; TRPM7; TRPC6; SK channel

The molecular identity of platelet Ca(2+) entry pathways is controversial. Furthermore, the extent to which Ca(2+)-permeable ion channels are functional in these tiny, anucleate cells difficult assess by direct electrophysiological measurements. Recent work has highlighted how primary megakaryocyte represents a bona fide surrogate for studies signalling, including patch clamp recordings ionic conductances. We have now screened all known members transient receptor potential (TRP) family non-selective cation murine megakaryocytes following individual selection rare marrow using glass micropipettes. RT-PCR detected messages TRPC6 and TRPC1, been reported platelets megakaryocytic cell lines, TRPM1, TRPM2 TRPM7, date not demonstrated megakaryocytic/platelet lineage. Electrophysiological presence constitutively active channel sensitive intracellular Mg(2+), TRPM2, an ADP-ribose-dependent activated oxidative stress. In addition, pharmacological properties stimulated physiological agonist ADP consistent with major role this G-protein-coupled receptor-dependent influx pathway. This study defines first time principal TRP within megakaryocyte, represent candidates diverse range stimuli megakaryocyte.