title: Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?
abstract: BACKGROUND
  Cation channels play an essential role in red blood cells (RBCs) ion homeostasis. One set of ion channels are the transient receptor potential channels of canonical type (TRPC channels). The abundance of these channels in primary erythroblasts, erythroid cell lines and RBCs was associated with an increase in intracellular Ca2+ upon stimulation with Erythropoietin (Epo). In contrast two independent studies on Epo-treated patients revealed diminished basal Ca2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet.
  
  
  METHODS
  To resolve the seemingly conflicting reports we challenged mature human and mouse RBCs of several genotypes with Epo and Prostaglandin E2 (PGE2) and recorded the intracellular Ca2+ content. Next Generation Sequencing was utilised to approach a molecular analysis of reticulocytes.
  
  
  CONCLUSIONS
  Our results allow concluding that Epo and PGE2 regulation of the Ca2+ homeostasis is distinctly different between murine and human RBCs and that changes in intracellular Ca2+ upon Epo treatment is a primary rather than a compensatory effect. In human RBCs, Epo itself has no effect on Ca2+ fluxes but inhibits the PGE2-induced Ca2+ entry. In murine mature RBCs functional evidence indicates TRPC4/C5 mediated Ca2+ entry activated by Epo whereas PGE2 leads to a TRPC independent Ca2+ entry.
authors.forename: Jens
authors.initials: J
authors.lastname: Danielczok
authors.forename: Laura
authors.initials: L
authors.lastname: Hertz
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruppenthal
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kaiser
authors.forename: Polina
authors.initials: P
authors.lastname: Petkova-Kirova
authors.forename: Anna
authors.initials: A
authors.lastname: Bogdanova
authors.forename: Elmar
authors.initials: E
authors.lastname: Krause
authors.forename: Peter
authors.initials: P
authors.lastname: Lipp
authors.forename: Marc
authors.initials: M
authors.lastname: Freichel
authors.forename: Lars
authors.initials: L
authors.lastname: Kaestner
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D015232:Dinoprostone / Q000494:pharmacology*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D051379:Mice; D061251:Primary Cell Culture; D013045:Species Specificity; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D050052:TRPC Cation Channels; D004921:Erythropoietin; D015232:Dinoprostone; D002118:Calcium
keywords: Calcuim-signalling; Erythropoietin; Prostaglandin E2; Red cells; TRPC channels