Molecular basis of R-type calcium channels in central amygdala neurons of the mouse

R-type Ca(2+) channels play a critical role in coupling excitability to dendritic Ca(2+) influx and neuronal secretion. Unlike other types of voltage-sensitive Ca(2+) channels (L, N, P/Q, and T type), the molecular basis for the R-type Ca(2+) channel is still unclear, thereby limiting further detailed analyses of R-type Ca(2+) channel physiology. The prevailing hypothesis is that α(1E) (Ca(V)2.3) gene encodes for R-type Ca(2+) channels, but the dearth of critical evidence has rendered this hypothesis controversial. Here we generated α(1E)-deficient mice (α(1E)−/−) and examined the status of voltage-sensitive Ca(2+) currents in central amygdala (CeA) neurons that exhibit abundant α(1E) expression and R-type Ca(2+) currents. The majority of R-type currents in CeA neurons were eliminated in α(1E)−/− mice whereas other Ca(2+) channel types were unaffected. These data clearly indicate that the expression of α(1E) gene underlies R-type Ca(2+) channels in CeA neurons. Furthermore, the α(1E)−/− mice exhibited signs of enhanced fear as evidenced by their vigorous escaping behavior and aversion to open-field conditions. These latter findings imply a possible role of α(1E)-based R-type Ca(2+) currents in amygdala physiology associated with fear.