Abstract
1. The effects of aluminium (Al) on calcium (Ca) currents were investigated by using the conventional two-electrode voltage clamp technique inHelix pomatia neurons. The peak amplitude, kinetics, and voltage dependence of activation and inactivation of the Ca currents were studied in the presence of 10−5−10−3 M AlCl3, at pH 6.
2. Al prolonged the rising phase of the Ca currents and therefore increased the time to peak at each command voltage step used.
3. There was no significant influence of Al on the peak amplitude of the Ca currents, but the voltage dependence of the time to peak, activation, and inactivation of the Ca currents shifted to more positive potentials as a consequence of Al treatment.
4. The leak currents were not influenced by Al up to 1 mM, which was the maximal dose applied.
5. The results support the suggestion that Al may modify the Ca homeostasis and that it exerts a neurotoxic effect, at least in part, by modulation of the Ca current of the neuronal membrane.
Key words: voltage clamp, molluscan neuron, Al treatment, Ca currents
References
- Banin, E., and Meiri, H. (1987). Impaired control of information transfer at an isolated synapse treated by aluminum: is it related to dementia?Brain. Res.423:359–363. [DOI] [PubMed] [Google Scholar]
- Banin, E., and Meiri, H. (1990). Toxic effects of alumino-silicates on nerve cells.Neuroscience39:171–178. [DOI] [PubMed] [Google Scholar]
- Birchall, J. D., and Chappell, J. S. (1988). Aluminium, chemical physiology, and Alzheimer's disease.LancetOct.29:1008–1010. [DOI] [PubMed] [Google Scholar]
- Brehm, P., and Eckert, R. (1978). Calcium entry leads to inactivation of calcium channel in Paramecium.Science202:1203–1206. [DOI] [PubMed] [Google Scholar]
- Candy, J. M., Oakley, A. E., and Klinowski, J. (1986). Aluminosilicates and senile plaque formation in Alzheimer's disease.Lancet2:354–357. [DOI] [PubMed] [Google Scholar]
- Crapper, D. R., and Dalton, A. J. (1973). Aluminium induced neurofibrillary degeneration, brain electrical activity and alterations in acquisition and retention.Physiol. Behav.10:935–945. [DOI] [PubMed] [Google Scholar]
- Crapper, D. R., and Tomko, J. G. (1975). Neuronal correlates of an encephalopathy associated with aluminium neurofibrillary degeneration.Brain Res.97:253–264. [DOI] [PubMed] [Google Scholar]
- Crapper, D. R., Quitkat, S., Krishnan, S. S., Dalton, A. J., and DeBoni, U. (1980). Intracellular aluminium content in Alzheimer's disease, dialysis encephalopathy and experimental aluminium encephalopathy.Acta Neuropathol.50:19–24. [DOI] [PubMed] [Google Scholar]
- Eckert, R., and Chad, J. E. (1984). Inactivation of calcium channels.Prog. Biophys. Mol. Biol.4:215–264. [DOI] [PubMed] [Google Scholar]
- Farnell, B. J., DeBoni, U., and Crapper-McLachlan, D. R. (1982). Aluminium neurotoxicity in the absence of meurofibrillary degeneration in CA1 hiopocampal pyramidal neurons.Exp. Neurol.78:241–258. [DOI] [PubMed] [Google Scholar]
- Farnell, B. J., Crapper-McLachlan, D. R., Bainbridge, K., DeBoni, U., Wong, L., and Wood, P. L. (1985). Calcium metabolism in aluminium encephalopathy.Exp. Neurol.88:68–83. [DOI] [PubMed] [Google Scholar]
- Garruto, R. M., Fukatsu, R., Yanagihara, R., Gajdusek, D. C., Hook, G., and Fiori, C. E. (1984). Imaging of calcium and aluminum neurofibrillary tangle-bearing neurons in parkisonism-dementia of Guam.Proc. Natl. Acad. Sci. USA81:1875–1879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ghetti, B., Musicco, M., Norton, J., and Bugiani, O. (1985). Nerve cell loss in the progressive encephalopathy induced by aluminium powder. A morphologic and semiquantitative study of the Purkinje cells.Neuropathol. Appl. Neurobiol.11:31–53. [DOI] [PubMed] [Google Scholar]
- Gulya, K., Rakonczay, A., and Kása, P. (1990). Cholinotoxic effect of aluminum in rat brain.J. Neurochem.54:1020–1026. [DOI] [PubMed] [Google Scholar]
- Hille, B. (1992).Ionic Channels of Excitable Membranes, 2nd ed. Sinauer Associates, Sunderland, MA. [Google Scholar]
- Klatzo, I., Wisniewski, H., and Streicher, E. (1965). Experimental production of neurofibrillary degeneration. I. Light microscopic observations.J. Neuropathol. Exp. Neurol.24:187–199. [DOI] [PubMed] [Google Scholar]
- Koenig, M. L., and Jope, R. S. (1987). Aluminum inhibits the fast phase of voltage-dependent calcium influx into synaptosomes.J. Neurochem.49:316–320. [DOI] [PubMed] [Google Scholar]
- Kostyuk, P. G., Veselovsky, N. S., and Fedulova, S. A. (1981). Ionic currents in the somatic membrane of rat dorsal root ganglion neurons.-II. Calcium currents.Neuroscience6:2431–2437. [DOI] [PubMed] [Google Scholar]
- Langui, D., Andertou, B. H., Brion, J. P., and Ulrich, J. (1988). Effects of aluminium chloride on cultured cells from rat brain hemispheres.Brain Res.438:67–76. [DOI] [PubMed] [Google Scholar]
- Martin, R. B. (1986). The chemistry of aluminum as related to biology and medicine.Clin. Chem.32:1797–1806. [PubMed] [Google Scholar]
- Meiri, H., and Shimoni, Y. (1991). Effects of aluminium on electrical and mechanical properties of frog atrial muscle.Br. J. Pharmacol.102:483–491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meiri, H., Banin, E., Roll, M., and Rousseau, A. (1993). Toxic effects of aluminium on nerve cells and synaptic transmission.Progr. Neurobiol.40:89–121. [DOI] [PubMed] [Google Scholar]
- Miller, C. A., and Levine, E. M. (1974). Effects of aluminum salts on cultured neuroblastoma cells.J. Neurochem.22:751–758. [DOI] [PubMed] [Google Scholar]
- Orrenius, S., McConkey, D. J., Bellomo, G., and Nicotera, P. (1989). Role of Ca2+ in toxic cell killing.TIPS10:281–285. [DOI] [PubMed] [Google Scholar]
- Perl, D. P., and Brody, A. R. (1980). Alzheimer's disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons.Science208:297–299. [DOI] [PubMed] [Google Scholar]
- Perl, D. P., Gajdusek, D. C., Garruto, R. M., Yanagihara, R. T., and Gibbs, C. J. (1982). Intraneuronal aluminum accumulation in amyotropic lateral sclerosis and parkinsonism-dementia of Guam.Science217:1053–1055. [DOI] [PubMed] [Google Scholar]
- Roll, M., Banin, E., and Meiri, H. (1989). Differentiated neuroblastoma cells are more susceptible to aluminium toxicity than developing cells.Arch. Toxicol.63:231–237. [DOI] [PubMed] [Google Scholar]
- Shi, B., and Haug, A. (1990). Aluminum uptake by neuroblastoma cells.J. Neurochem.55:551–558. [DOI] [PubMed] [Google Scholar]
- Siegel, N., and Haug, A. (1983). Aluminum interaction with calmodulin. Evidence for altered structure and function from optical and enzymatic studies.Biochim. Biophys. Acta744:36–45. [DOI] [PubMed] [Google Scholar]
- Suhayda, C. G., and Haug, A. (1984). Organic acids prevent aluminum-induced conformational changes in calmodulin.Biochem. Biophys. Res. Commun.119:376–381. [DOI] [PubMed] [Google Scholar]
- Tillotson, D. (1979). Inactivation of Ca conductance dependent on entry of Ca ions in molluscan neurons.Proc. Natl. Acad. Sci. USA76:1497–1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wisniewski, H. M., Shek, J. W., Gruca, S., and Sturman, J. A. (1984). Aluminium induced neurofibrillary changes in axons and dendrites.Acta. Neuropathol.63:190–197. [DOI] [PubMed] [Google Scholar]
- Yates, C. M., Simpson, J., Russell, D., and Gordon, A. (1980). Cholinergic enzymes in neurofibrillary degeneration produced by aluminium.Brain Res.197:269–274. [DOI] [PubMed] [Google Scholar]
