TRPM2 Channel Membrane Currents in Primary Rat Megakaryocytes Were Activated by the Agonist ADP-Ribose but Not Oxidative Stress


Naziroglu M.

JOURNAL OF MEMBRANE BIOLOGY, vol.241, no.2, pp.51-57, 2011 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 241 Issue: 2
  • Publication Date: 2011
  • Doi Number: 10.1007/s00232-011-9356-8
  • Journal Name: JOURNAL OF MEMBRANE BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.51-57
  • Süleyman Demirel University Affiliated: Yes

Abstract

Melastatin-like transient receptor potential 2 (TRPM2) channel activation/inhibition mechanisms in response to ADP-ribose (ADPR), oxidative stress, flufenamic acid (FFA) and 2-aminoethoxydiphenyl borate (2-APB) are not clear. We tested the effects of FFA and 2-APB on ADPR-induced TRPM2 cation channel currents in rat native bone marrow megakaryocytes. Megakaryocyte cells were freshly isolated from rat bone marrow and studied with the conventional whole-cell patch-clamp technique. Extracellular H(2)O(2), FFA and 2-APB were added through the patch chamber, while intracellular ADPR was applied through the pipette. Nonselective cation currents were consistently induced by ADPR but not H(2)O(2). Current density of ADPR in the cells was significantly (P < 0.001) higher than in control. The time courses of ADPR effects in the megakaryocytes were characterized by a delay of 2.24 +/- 0.73. The ADPR-induced Ca(2+) gate was not blocked by either the IP(3) receptor inhibitor 2-APB or the PLC inhibitor FFA. In conclusion, TRPM2 channels were constitutively activated by intracellular ADPR, although the channel currents in rat native megakaryocytes were not affected by extracellular H(2)O(2), 2-APB or FFA. Activation of TRPM2 channels in megakaryocytes seems to be intracellular and ADPR-dependent.