Figure 4.

Inhibition of CaM kinase II α subunit expression correlates with increased neuronal excitability. (A) CaM kinase II α subunit antisense oligonucleotide exposure resulted in inhibition of CaM kinase II α subunit expression and increased spike frequency. Both spike frequency (●) and decreased immunoreactivity of CaM kinase II α subunit protein (▴) were measured as a function of time of CaM kinase II α subunit antisense oligonucleotide exposure in the same cultures. A significant increase in spike frequency and inhibition of CaM kinase II α subunit expression was not observed until 2 days of antisense oligonucleotide exposure, and maximal inhibition of kinase expression and spike frequency were observed after 2.5–3 days of oligonucleotide exposure. (*, P < 0.001 different from missense control, n = 4, one-way ANOVA). (B) Correlation between inhibition of CaM kinase II α subunit enzyme expression and increased neuronal excitability. Linear regression analysis contrasting inhibition of CaM kinase II α subunit expression and increased spike frequency was performed. Both inhibition of CaM kinase II α subunit expression and spike frequency were measured in the same cultures (data are expressed as means ± SEM for an n = 4). Inhibition of CaM kinase II α subunit expression correlated with increased spike frequency with an r² = 0.945.