TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy.

Background: Mossy 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.

Results: Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated non-selective cation channel regulating diverse physiological functions of excitable cells.

Functionally active TRPA1 ion channel is downregulated in peptidergic neurons of the Edinger-Westphal nucleus upon acute alcohol exposure.

The centrally projecting Edinger-Westphal nucleus (EWcp) contributes to the control of alcohol consumption by its urocortin 1 (UCN1) and cocaine- and amphetamine-regulated transcript (CART) co-expressing peptidergic neurons. Our group recently showed that the urocortinergic centrally projecting EWcp is the primary seat of central nervous system transient receptor potential ankyrin 1 (TRPA1) cation channel mRNA expression. Here, we hypothesized that alcohol and its metabolites, that pass through the blood-brain barrier, may influence the function of urocortinergic cells in centrally projecting EWcp by activating TRPA1 ion channels.

TRPM4 inhibition by meclofenamate suppresses Ca2+-dependent triggered arrhythmias.

Aims: Cardiac arrhythmias are a major factor in the occurrence of morbidity and sudden death in patients with cardiovascular disease. Disturbances of Ca2+ homeostasis in the heart contribute to the initiation and maintenance of cardiac arrhythmias. Extrasystolic increases in intracellular Ca2+ lead to delayed afterdepolarizations and triggered activity, which can result in heart rhythm abnormalities.

Mossy cells of the dentate gyrus: Drivers or inhibitors of epileptic seizures?

Mossy cells (MCs) are glutamatergic cells of the dentate gyrus with an important role in temporal lobe epilepsy. Under physiological conditions MCs can control both network excitations via direct synapses to granule cells and inhibition via connections to GABAergic interneurons innervating granule cells. In temporal lobe epilepsy mossy cell loss is one of the major hallmarks, but whether the surviving MCs drive or inhibit seizure initiation and generalization is still a debate.