Ca²⁺‐dependent induction of TRPM2 currents in hippocampal neurons

Abstract

TRPM2 is a Ca2+ -permeable member of the transient receptor potential melastatin family of cation channels whose activation by reactive oxygen/nitrogen species (ROS/RNS) and ADP-ribose (ADPR) is linked to cell death. While these channels are broadly expressed in the CNS, the presence of TRPM2 in neurons remains controversial and more specifically, ] i , activation of NMDA receptors (NMDARs), which are highly permeable to Ca 2+ , was also permissive for current development. Importantly, given the prominent vulnerability of CA1 neurons to free-radical-induced cell death, we confirmed that, with ADPR in the pipette, a brief application of NMDA could evoke a large inward current in CA1 pyramidal neurons from hippocampal slices that was abolished by the removal of extracellular Ca 2+ , consistent with TRPM2 activation. Such a current was absent in interneurons of CA1 stratum radiatum. Finally, infection of cultured hippocampal neurons with a TRPM2-specific short hairpin RNA (shRNA TRPM2 ) significantly reduced both the expression of TRPM2 and the amplitude of the ADPR-dependent current. Taken together, these results indicate that hippocampal pyramidal neurons possess functional TRPM2 channels whose activation by ADPR is functionally coupled to VDCCs and NMDARs through a rise in [Ca 2+ ] i

Possible Involvement of Transient Receptor Potential Channels in Electrophile-Induced Insulin Secretion from RINm5F Cells

“…These results suggest that the stimulation of TRPA1 eventually induces VDCC activation, and thereby increases in Ca 2+ influx. An association between TRP channels and VDCC has been reported in diverse systems, [38][39][40][41] including β-cells, 42) which showed that lowering the extracellular Na + concentration inhibited an islet amyloid polypeptide-stimulated TRPV4-mediated increase in [Ca 2+ ] i in cultured MIN6 β-cells. As TRPV4 is permeable to Ca 2+ and Na + to a similar extent, 43) the authors of that study concluded that islet amyloid polypeptide induces Na + entry via TRPV4, which thus stimulates membrane depolarization and Ca 2+ entry through VDCC.…”

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

“…A Cl − channel inhibitor, DIDS (100 μM), did not inhibit the current (data not shown), indicating that the current is not a Cl − current. CLT is an inhibitor of a non-selective cation current through the TRPM2 channel (21,22). When we tested 10 μM CLT, the current in normoxia-exposed fibroblasts were only slightly inhibited (Fig.…”

Redox regulation of calcium ion channels: Chemical and physiological aspects

“…TRPM2 knock-out mice are protected against this infiltration and show reduced inflammation in a mouse model of colitis ulcerosa [131]. Neurons also express TRPM2 where it may be involved in H 2 O 2 -induced neuronal death [132,133].…”