FIGURE 1.

Potential roles of astrocytic Ca²⁺ signaling in epilepsy. Strong astrocytic Ca²⁺ signals have been shown to occur in the emergency of acute seizures (in ictogenesis), that are probably triggered by neurotransmitters released by neurons. Ca²⁺ increases at the onset of seizures are known to be partly mediated by release through IP₃R2 from the endoplasmic reticulum, even though pronounced Ca²⁺ signaling is present also in mice devoid of IP₃R2. It is thought that intracellular Ca²⁺ increases may trigger proconvulsive gliotransmitter release. In astrocytic endfeet, increased Ca²⁺ signaling has been shown to correlate with ictal vasodilation. Epileptogenesis triggers a pronounced increase in mGluR5 expression, mGluR5-mediated Ca²⁺ signaling, and increased glutamate uptake. An increase in astrocytic Ca²⁺ signaling has been demonstrated in the days after status epilepticus, and aberrant Ca²⁺ signaling at later time points in the epileptogenesis has been anecdotally reported. Increased Ca²⁺ signaling could potentially cause both the release of glutamate (pro-convulsive), purines (pro-convulsive), and GABA (anti-convulsive, through Bestrophin-1 channels). In astrocytic endfeet in epileptic tissue a pronounced loss of aquaporin-4 (AQP4) and the K⁺ inwardly rectifying channel Kir4.1 can potentially be due to Ca²⁺ activated proteases causing a disassembly of the dystrophin associated protein complex (DAPC) tethering AQP4 and Kir4.1 to perivascular endfeet.