title: Up-Regulation of Na+/Ca2+ Exchange in Megakaryocytes Following TGFβ1 Treatment.
abstract: 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.
authors.affiliation: Department of Cardiology, Vascular Medicine and Physiology, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Almilaji
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Hosseinzadeh
authors.forename: Evi
authors.initials: E
authors.lastname: Schmid
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D016257:Fura-2 / Q000737:chemistry / Q000378:metabolism; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019831:Sodium-Calcium Exchanger; D053773:Transforming Growth Factor beta1; C110374:sodium-calcium exchanger 1; D012964:Sodium; D011188:Potassium; D002118:Calcium; D016257:Fura-2