Recent developments on molecular mechanisms role on activation of TRPM2 cation channels

Transient receptor potential (trp) channels were first described in drosphila, where photoreceptor carrying trp gene mutations exhibit a transient voltage response to continuous light. these are subdivided into six major subgroups. melastatin (or long) trp channels (trpm2) are nonspecific for ca2+. we have become particularly interested in one member of latter family, known as trpm2, for a number of reasons a potential role in cell death resulting from oxidative stress. several mechanisms such as adp-ribose (adpr) and oxidative stres have been proposed for oxidant-mediated ca2+ fluxes, including trp channels. activation of trpm2 currents have been recorded upon exposure to adpr as measured by ca2+ influx using electrophysiological measurements in intact cells as well as in patch-clamp experiments. additional experimental evidence from several groups shows that oxidative stress results in ca2+ influx through trpm2 opening, and consequently, ca2+ dependent cell death. however, an important unanswered question is whether oxidantinduced gating of trpm2 occurs directly at the membrane induced by h2o2 binding to trpm2, or indirectly through production of the second messenger adpr.