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 _v2.3) 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.