Calcium channels: critical targets of toxicants and diseases.

Abstract

The structure and regulation of voltage-dependent calcium channels and their role ininherited and toxicant-induced neurologicdisorders was the topic of a conference spon-sored and hosted by the National Institute ofEnvironmental Health Sciences, the U.S.Environmental Protection Agency, SibiaNeurosciences, and the Muscular DystrophyAssociation on 6–8 December 1999. Theconference, “Calcium Channels: CriticalTargets of Toxicants and Diseases,” broughttogether experts in a variety of disciplines todiscuss our current knowledge of calciumchannel structure and function, channel reg-ulation by intracellular signaling molecules,and the effects of mutations, aging, and toxi-cants on channel function.Calcium channels play important anddiverse roles in neurologic function. It hasbeen known for many years that calciumchannels are likely targets of a variety oforganic and inorganic toxicants. More recent-ly, calcium channel mutations have beenimplicated in several inherited neurologic dis-orders, including migraine headaches, variousmovement disorders, and some types ofmalignant hyperthermia. The last decade hasseen great strides in determining the subunitstructure of calcium channels, how the genet-ic diversity of subunits generates a variety offunctionally distinct channels, and how intra-cellular signaling pathways regulate channelfunction. The meeting was convened to guidefuture research by applying this knowledge ofcalcium channel biology to further our under-standing of how toxicants and mutations alterchannel functions. The presentations discussed four majoraspects of calcium channels that are relevantfor understanding their roles in genetic andenvironmental neurologic disorders: thegenetics and molecular biology of channelstructure; interactions between calcium chan-nels and intracellular signaling pathways; theeffects of toxicants on calcium channel func-tion, both through direct interactions withchannel subunits and by altering intracellularsignaling; and the genetics, molecular biolo-gy, and physiology of inherited disorderscaused by mutations in the genes encodingcalcium channel subunits or from autoim-mune disorders caused by the generation ofantibodies against subunits of those proteins.