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


CONCLUSIONS
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.
Chen
Lei
L
Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Liu
Chang-jin
CJ
Tang
Ming
M
Li
Ai
A
Hu
Xin-wu
XW
Du
Yi-mei
YM
Shen
Jing-jing
JJ
Lu
Yong-li
YL
Heschler
Jurgen
J
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002469:Cell Separation; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D007783:Lactones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D017607:Aluminum Compounds; D015220:Calcium Channels; D002712:Chlorides; D004224:Diterpenes; D046934:Ginkgolides; D007546:Isoquinolines; D007783:Lactones; D018696:Neuroprotective Agents; D013449:Sulfonamides; D005576:Colforsin; D000077410:Aluminum Chloride; C045856:ginkgolide B; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide