title: Aluminum inhibits the fast phase of voltage-dependent calcium influx into synaptosomes.
abstract: Aluminum has been shown to have neurotoxic effects, but the mechanisms by which it acts are not well understood. Because it has been reported that aluminum can interact with Ca2+-binding sites, the possibility that aluminum might interfere with Ca2+ influx into synaptosomes was examined. At concentrations of 50 microM and greater, aluminum significantly inhibited the fast phase (0-1 s) of the voltage-dependent uptake of 45Ca2+ into synaptosomes. Higher concentrations of aluminum also reduced 45Ca2+ uptake measured at 1 s in nondepolarizing media and inhibited the slow phase of 45Ca2+ uptake into synaptosomes whether they were suspended in either low K or high K media. The possibility that aluminum competitively inhibits the fast phase of Ca2+ influx was investigated. Aluminum (250 microM) increased the apparent KT (concentration of Ca2+ at which Ca2+ transport is half maximal) for 45Ca2+ of fast phase voltage-dependent channels and slightly decreased the maximal influx (Jmax). These effects are characteristic of a mixed type inhibitor, and the apparent Ki for Al3+ is estimated to be 0.64 mM. The interaction of aluminum with the fast phase of voltage-dependent calcium influx may disrupt intraneuronal calcium homeostasis and may also represent a means by which aluminum could accumulate intraneuronally.
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007473:Ion Channels; D000535:Aluminum; D002118:Calcium