<b><i>Background:</i></b> It is well established that reactive astrocytes express L-type calcium channels (LTCC), but their functional role is completely unknown. We have recently shown that reactive astrocytes highly express the Ca_V1.2 α₁-subunit around β-amyloid (Aβ) plaques in an Alzheimer mouse model. The aim of the present study was to explore whether Aβ peptides may regulate the mRNA expression of all LTCC subunits in primary mouse astrocytes in culture. <b><i>Methods:</i></b> Confluent primary astrocytes were incubated with 10 µg/ml of human or murine Aβ or the toxic fragment Aβ_25-35 for 3 days or for 3 weeks. The LTCC subunits were determined by quantitative RT-PCR. <b><i>Results:</i></b> Our data show that murine Aβ₄₂ slightly but significantly increased Ca_V1.2 and Ca_V1.3 expression when incubated for 3 days. This acute treatment with murine Aβ enhanced β₂ and β₃ mRNA levels but decreased α₂δ-2 mRNA expression. When astrocytes were incubated for 3 weeks, the levels of Ca_V1.2 α₁ were significantly decreased by the murine Aβ and the toxic fragment. As a control, the protein kinase C-ε activator DCP-LA displayed a decrease in Ca_V2.1 expression. <b><i>Conclusion:</i></b> In conclusion, our data show that Aβ can differentially regulate LTCC expression in primary mouse astrocytes depending on incubation time.