Effects of toxic environmental contaminants on voltage-gated calcium channel function: from past to present.
Voltage-gated Ca2+ channels are targets of the number of naturally occurring toxins, therapeutic agents as well as environmental toxicants. Because of similarities of their chemical structure to Ca2+ in terms of hydrated ionic radius, electron orbital configuration, or other chemical properties, polyvalent cations from aluminum to zinc variously interact with multiple types of voltage-gated Ca2+ channels. These nonphysiological metals have been used to study the structure and function of the Ca2+ channel, especially its permeability characteristics. Two nonphysiological cations, Pb2+ and Hg2+, as well as their organic derivatives, are environmental neurotoxicants which are highly potent Ca2+ channel blockers. These metals also apparently gain intracellular access in part by permeating through Ca2+ channels. In this review the history of Ca2+ channel block produced by Pb2+ and Hg2+ as well as other nonphysiological cations is traced. In particular the characteristics of Ca2+ channel block induced by these environmental neurotoxic metals and the consequences of this action for neuronal function are discussed.
Atchison
William D
WD
Neuroscience Program, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA. atchiso1@msu.edu
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000633:toxicity*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D004785:Environmental Pollutants / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007854:Lead / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008628:Mercury / Q000633:toxicity*; D008670:Metals / Q000633:toxicity; D016062:Porosity / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004785:Environmental Pollutants; D008670:Metals; D007854:Lead; D008628:Mercury; D002118:Calcium