Drug effects on calcium homeostasis in mouse CA1 hippocampal neurons.
Voltage-dependent Ca2+ channels (VDCC) are important in control of neuronal excitability, synaptic transmission, and many other cellular process. Even the slightest alteration in Ca2+ currents can have a considerable impact on the neuronal function. However, it is still unknown whether Ca2+ currents are affected by neurotoxic drugs such as lead, cobalt, zinc, cadmium, thallium, lanthanum, and aluminum. We have characterized the effects of neurotoxic drugs on Ca2+ homeostasis in CA1 hippocampal C57BL mice. Fura 2-AM fluorescence photometry was used to measure intracellular Ca2+ concentration ([Ca2+]i) in the presence and absence of neurotoxic drugs (10 microM) in response to KCl application. The peak [Ca2+]i due to KCl application was reduced in the presence of lead (60%), cobalt (35%), zinc (62%), cadmium (71%), thallium (27%), and lanthanum (66%). By contrast, in the presence of aluminum the peak [Ca2+]i was either increased (46%) or it was not affected. These results indicate that neurotoxic drugs could block the entry of calcium into CA1 neurons via VDCC.
Alshuaib
Waleed B
WB
Department of Physiology, Faculty of Medicine, Kuwait University, Safat, Kuwait. waleed@hsc.kuniv.edu.kw
Cherian
Susan P
SP
Hasan
Mohamed Y
MY
Fahim
Mohamed A
MA
D000535:Aluminum / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000031:analogs & derivatives* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D019216:Metals, Heavy / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D013997:Time Factors
D005456:Fluorescent Dyes; D019216:Metals, Heavy; C049925:fura-2-am; D011189:Potassium Chloride; D000535:Aluminum; D002118:Calcium; D016257:Fura-2