Synergistic regulation of endogenous TRPM2 channels by adenine dinucleotides in primary human neutrophils.

ABSTRACT: The Ca(2+)-permeable TRPM2 channel is a dual function protein that is activated by intracellular ADPR through its enzymatic pyrophosphatase domain with Ca(2+) acting as a co-factor. Other TRPM2 regulators include cADPR, NAADP and H(2)O(2), which synergize with ADPR to potentiate TRPM2 activation. Although TRPM2 has been thoroughly characterized in overexpression or cell-line systems, little is known about the features of TRPM2 in primary cells. We here characterize the regulation of TRPM2 activation in human neutrophils and report that ADPR activates TRPM2 with an effective half-maximal concentration (EC(50)) of 1microM. Potentiation by Ca(2+) is dose-dependent with an EC(50) of 300nM. Both cADPR and NAADP activate TRPM2, albeit with lower efficacy than in the presence of subthreshold leve

SUBMITTER: Lange I 

PROVIDER: S-EPMC2597220 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature