Abstract： Whole-cell patch clamp recording was used to investigate the action of β-amyloid peptide1-40 (Aβ1-40) on high voltageactivated calcium channel current (IHVA) in acutely isolated hippocampal CA1 pyramidal neurons in rats and observe its modulation by ginkgolide B (GB). Drug was applied by extracellular bath or adding in the pipette solution, and its effect was determined by comparing the amplitude of IHVA before and after the drug application. Bath application of aggregated Aβ1-40 at concentrations of 0.01 ～30 μmol/L increased the amplitude of IHVA in a dose-dependent manner by (5.43+3.01)% (n=8, P＞0.05), (10.49+4.13)% (n=11, P＞0.05), (40.69+8.01)% (n=16, P＜0.01), (58.32+4.85)% (n=12, P＜0.01), and (75.45+5.81)% (n=6, P＜0.01), respectively, but had no effect on the I-V curve of IHVA; fresh Aβ1-40 almost had no effect on IHVA (n=5, P＞0.05). L-type calcium channel antagonist nifedipine abolished the increase of IHVA by Aβ1-40. The increase of IHVA by Aβ1-40 (1.0 μmol/L) was enhanced to (66.19+5.74)% (P＜0.05) by 8-Br-cAMP (membrane permeable analogue of cAMP) and to (73.21 +6.90)% (P＜0.05) by forskolin, an adenylyl cyclase (AC) agonist, and reduced to (20.08+2.18)% (P＜0.05) by H-89, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) antagonist. GB effectively inhibited the increase of IHVA by Aβ1-40. The results indicate that Aβ1-40 leads to an intracellular calcium overload by increasing IHVA via AC-cAMP-PKA. This may be one of the mechanisms for its neurotoxicity. GB can prevent neurons from neurotoxicity by inhibiting abnormal calcium influx caused by Aβ1-40.