Open AccessH 2 O 2 ‐induced Ca 2+ influx and its inhibition by N‐(p‐amylcinnamoyl) anthranilic acid in the β‐cells: involvement of TRPM2 channels
Author(s) -
Bari Muhammad R.,
Akbar Sanian,
Eweida Mohamed,
Kühn Frank J.P.,
Gustafsson Amanda Jabin,
Lückhoff Andreas,
Islam Md. Shahidul
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00737.x
Subject(s) - trpm2 , transient receptor potential channel , chemistry , biochemistry , biophysics , microbiology and biotechnology , receptor , biology
Type 2 melastatin‐related transient receptor potential channel (TRPM2), a member of the melastatin‐related TRP (transient receptor potential) subfamily is a Ca 2+ ‐permeable channel activated by hydrogen peroxide (H 2 O 2 ). We have investigated the role of TRPM2 channels in mediating the H 2 O 2 ‐induced increase in the cytoplasmic free Ca 2+ concentration ([Ca 2+ ] i ) in insulin‐secreting cells. In fura‐2 loaded INS‐1E cells, a widely used model of β‐cells, and in human β‐cells, H 2 O 2 increased [Ca 2+ ] i , in the presence of 3 mM glucose, by inducing Ca 2+ influx across the plasma membrane. H 2 O 2 ‐induced Ca 2+ influx was not blocked by nimodipine, a blocker of the L‐type voltage‐gated Ca 2+ channels nor by 2‐aminoethoxydiphenyl borate, a blocker of several TRP channels and store‐operated channels, but it was completely blocked by N‐(p‐amylcinnamoyl)anthranilic acid (ACA), a potent inhibitor of TRPM2. Adenosine diphosphate phosphate ribose, a specific activator of TRPM2 channel and H 2 O 2 , induced inward cation currents that were blocked by ACA. Western blot using antibodies directed to the epitopes on the N‐terminal and on the C‐terminal parts of TRPM2 identified the full length TRPM2 (TRPM2‐L), and the C‐terminally truncated TRPM2 (TRPM2‐S) in human islets. We conclude that functional TRPM2 channels mediate H 2 O 2 ‐induced Ca 2+ entry in β‐cells, a process potently inhibited by ACA.