title: Contributions of Ca2+ and Zn2+ to spreading depression-like events and neuronal injury.
abstract: The phenomenon of spreading depression (SD) involves waves of profound neuronal and glial depolarization that spread throughout brain tissue. Under many conditions, tissue recovers full function after SD has occurred, but SD-like events are also associated with spread of injury following ischemia or trauma. Initial large cytosolic Ca2+ increases accompany all forms of SD, but persistently elevated Ca2+ loading is likely responsible for neuronal injury following SD in tissues where metabolic capacity is insufficient to restore ionic gradients. Ca2+ channels are also involved in the propagation of SD, but the channel subtypes and cation fluxes differ significantly when SD is triggered by different types of stimuli. Ca2+ influx via P/Q type channels is important for SD generated by localized application of high K+ solutions. In contrast, SD-like events recorded in in vitro ischemia models are not usually prevented by Ca2+ removal, but under some conditions, Zn2+ influx via L-type channels contributes to SD initiation. This review addresses different roles of Ca2+ in the initiation and consequences of SD, and discusses recent evidence that selective chelation of Zn2+ can be sufficient to prevent SD under circumstances that may have relevance for ischemic injury.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-0001, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Dietz
authors.forename: John H
authors.initials: JH
authors.lastname: Weiss
authors.forename: C William
authors.initials: CW
authors.lastname: Shuttleworth
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D013181:Cortical Spreading Depression / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000473:pathology*; D015032:Zinc / Q000378:metabolism / Q000502:physiology*
chemical_list: D002614:Chelating Agents; D015032:Zinc; D002118:Calcium