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 (IHVA) 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: A1 0.1mmol/L (low concentration) reduced IHVA; Al 0.75 and 1.0mmol/L (high concentrations) increased IHVA, and Al decreased and increased IHVA at intermediate concentrations of 0.25 and 0.5mmol/L. The increase of IHVA by Al 1.0mmol/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 0.1mmol/L was neither reversed by forskolin nor affected by H-89. Gin B had no effect on IHVA in normal neurons,but canceled the increase in IHVA by 1.0mmol/L Al. Conclusion: The results indicate that the mechanism of Al affecting IHVA differs at different concentrations,and this may be attributed to its complex actions. Gin B could prevent neurons from injury by inhibiting calcium influx.