Transient receptor potential melastatin 4 (TRPM4) regulates hilar mossy cell loss in temporal lobe epilepsy

Abstract

ABSTRACTMossy cells comprise a large fraction of excitatory neurons in the hippocampal dentate gyrus and their loss is one of the major hallmarks of temporal lobe epilepsy (TLE). The vulnerability of mossy cells in TLE is well known in animal models as well as in patients, however the mechanisms leading to cellular death is unclear. One possible explanation for their sensitivity is linked to their specific ion channel composition. TRPM4 is a Ca2+-activated non-selective cation channel regulating diverse physiological function of excitable cells. Here, we identified that TRPM4 is present and functionally active in hilar mossy cells. Furthermore, we showed that TRPM4 contributes to mossy cells death following status epilepticus and therefore modulates seizure susceptibility and epilepsy-related memory deficits in the chronic phase of TLE.