Action of aluminum on high voltage-dependent calcium current and its modulation by ginkgolide B.

Aim: To investigate the effect of aluminum (Al) on high voltage-dependent calcium current (I(HVA)) and its modulation by ginkgolide B (Gin B).

Methods: The whole-cell, patch-clamp technique was used to record IHVA from acutely isolated hippocampal CA1 pyramydal neurons in rats.

Results: Al 0.1 mmol/L (low concentration) reduced I(HVA); Al 0.75 and 1.0 mmol/L (high concentrations) increased I(HVA), and Al decreased and increased I(HVA) at intermediate concentrations of 0.25 and 0.5 mmol/L. The increase of I(HVA) by Al 1.0 mmol/L was enhanced by the adenylyl cyclase (AC) agonist forskolin and was partly abolished by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) antagonist H-89, whereas the decrease observed with Al 0.1 mmol/L was neither reversed by forskolin nor affected by H-89. Gin B had no effect on I(HVA) in normal neurons, but canceled the increase in I(HVA) by 1.0 mmol/L Al.

Conclusion: The results indicate that the mechanism of Al affecting I(HVA) differs at different concentrations, and this may be attributed to its complex actions. Gin B could prevent neurons from injury by inhibiting calcium influx.