<f>Aβ</f>(25–35) and <f>Aβ</f>(1–40) act on different calcium channels in CA1 hippocampal neurons

The acute effects of <f>β</f>-amyloid (25–35) and (1–40) on high voltage activated calcium channels were compared in CA1 pyramidal cells of adult mouse hippocampal slices using the whole-cell patch-clamp recording. Bath application of oligomeric <f>β</f>-amyloid (25–35) reversibly increased the barium current (IBa) to 1.61 (normalized amplitude), while oligomeric <f>β</f>-amyloid (1–40) reversibly enhanced the IBa to 1.74. Reverse-sequence <f>β</f>-amyloid [(35–25) and (40–1)] had no effect. The effect of <f>β</f>-amyloid (25–35) was blocked by nifedipine, a selective antagonist of L-type calcium channels. In contrast, the effect of <f>β</f>-amyloid (1–40) was not blocked by nifedipine and IBa was enhanced to 4.96. It is concluded that these oligomeric peptides may act through different types of calcium channels and/or receptors. The toxicity of <f>Aβ</f>(25–35) implicates a potentiation of L-type calcium channels while the one of <f>Aβ</f>(1–40) is related to an increase of non-L-type calcium channels, which may involve an increase in transmitter release. [Copyright &y& Elsevier]