Figure 5.

Multiple cortical spreading depolarizations associated with induced seizures followed by death in homozygous Cacna1a^S218L mice. Representative ECoG (AC and DC) recordings showing that stimulation (shaded grey) was followed by afterdischarges in all wild-type (WT) mice (7/7; example in A) and heterozygous Cacna1a^S218L (het S218L) mice (9/9; example in B), while only in a minority of homozygous Cacna1a^S218L (hom S218L) mice [2/11; example in C(i)], as indicated by insets (corresponding to the shaded red time windows). Cortical spreading depolarization (indicated by arrowheads in example traces) was observed directly following afterdischarges in all but one heterozygous Cacna1a^S218L mice. In homozygous Cacna1a^S218L mice, multiple cortical spreading depolarizations occurred, followed by a terminal depolarization [C(ii); TD; indicated by an arrow]. Fatal outcome was observed in 7 of 11 homozygous Cacna1a^S218L mice but none of the wild-type and heterozygous Cacna1a^S218L mice. AC = alternating current; DC = direct current.