A relative energy failure is associated with low-Mg2+ but not with 4-aminopyridine induced seizure-like events in entorhinal cortex

During seizure-like events (SLEs), intracellular Ca2+ concentration ([Ca2+] (i)) increases causing depolarization of the mitochondrial membrane and sub sequent intramitochondrial accumulation of Ca2+. Mitochondrial depolarizati on results in an interruption of oxidative phosphorylation and increase in reactive oxygen species. Calcium activates enzymes of the citrate cycle. A characteristic feature of the low-Mg2+-induced SLEs is that they are transf ormed to a late activity refractory to anticonvulsant drugs, which may be r egarded as a model system of difficult to treat status epilepticus. In cont rast, 4-aminopyridine (4-AP)-induced activity rarely evolves to such late a ctivity. The autofluorescence of NAD(P)H was used to monitor changes in cel lular energy metabolism in the entorhinal cortex in two in vitro models of focal epilepsy. During repetitive 4-AP-induced SLEs there was a short decre ase followed by a long-lasting overshoot of the NAD(P)H signal. This sequen ce remained unaltered during recurring SLEs. In contrast, during recurrent low-Mg2+-induced SLEs, the brief initial NADH signal reduction was unchange d but the following overshoot of NADH displayed a continuous decrease. This indicates a relative energy failure, which may contribute to the transform ation to late activity in the low-Mg2+ model.