Fig. (3) Functional implications of Cav2.3 R-type VGCC in cellular epileptiform activity, excitotoxicity and thetagenesis. Cav2.3 mediated Ca2+ influx triggers varies intracellular cascades. One cascade mediates the activation of cyclic-nucleotide gated channels leading to plateau potentials and superimposed bursting. Associated hyperexcitability and Ca2+ overload can result in excitotoxicity and neuronal apoptosis. Note that Cav2.3 Ca2+ channels are modulated by muscarinic signaling. The G αq11, DAG and PKC pathway was reported to be associated with thetagenesis as well (reprinted from ).