CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

► Mutations in CaV2.1 Ca2+ channels cause familial hemiplegic migraine type 1 (FHM1). ► CaV2.1 channels with the human FHM1 mutations activate at more hyperpolarizing potentials. ► FHM1 generates a gain-of-function in synaptic transmission, affecting also synaptic plasticity. ► FHM1 increases the susceptibility for cortical spreading depression (CSD).