Proceedings of the National Academy of Sciences of the United States of America vol. 99, no. 5, pp. 3276 - 3281
SCI; SCIE; SCOPUS
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.