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.
Neuroscience Program, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA. atchiso1@msu.edu
William D
WD
Atchison
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