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Up-Regulation of Na+/Ca2+ Exchange in Megakaryocytes Following TGFβ1 Treatment
Ahmad Almilaji1, Jing Yan, Zohreh Hosseinzadeh
1Department of Cardiology, Vascular Medicine and Physiology, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany.
Background:
Blood platelets are activated by increase of cytosolic Ca2+ activity ([Ca2+]i). Ca2+ entry is accomplished in part by store operated Ca2+ entry (SOCE) involving Ca2+ release activated Ca2+-channel (CRAC) moiety Orai1 and its regulator STIM1, which are stimulated by depletion of intracellular Ca2+ stores. An increase of [Ca2+]i is terminated by Na+/Ca2+-exchange. The expression of both, Orai1 and STIM1 in megakaryocytes is up-regulated by tumor growth factor TGFβ1, a powerful regulator of megakaryocyte differentiation. The present study explored whether TGFβ1 similarly modifies megakaryocyte Na+/Ca2+-exchanger activity.
Methods:
[Ca2+]i was determined utlizing Fura-2 fluorescence, SOCE from increase of [Ca2+]i, following readdition of extracellular Ca2+ after store depletion, and Na+/Ca2+-exchanger activity from increase of [Ca2+]i and whole cell currents following removal of extracellular Na+.
Results:
TGFβ1 treatment not only augments the increase of [Ca2+]i following store depletion and SOCE, but significantly up-regulates Na+/Ca2+-exchanger activity as apparent from [Ca2+]i measurements and whole cell currents.
Conclusions:
TGFβ1 is a powerful stimulator of both, SOCE and Na+/Ca2+-exchanger activity in megakaryocytes.
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