The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization.
Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little of how cell volume affects neuronal dynamics. We here performed the first detailed study of the effects of cell volume on neuronal dynamics. By incorporating cell swelling together with dynamic ion concentrations and oxygen supply into Hodgkin-Huxley type spiking dynamics, we demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. Our use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial K buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia. We argue that the dynamics of seizures, spreading depression, and anoxic depolarization lie along a continuum of the repertoire of the neuron membrane that can be understood only when the dynamic ion concentrations, oxygen homeostasis,and cell swelling in response to osmotic pressure are taken into consideration. Our results demonstrate the feasibility of a unified framework for a wide range of neuronal behaviors that may be of substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states.
Department of Physics, University of South Florida, Tampa, Florida 33620, United States of America.
Ghanim
G
Ullah
Department of Cell Biology and Neuroscience, University of California, Riverside, California 92501 United States of America.
Yina
Y
Wei
Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
Markus A
MA
Dahlem
School of Mathematics and Statistics, University of Sydney, New South Wales, 2006, Australia.
Martin
M
Wechselberger
Center for Neural Engineering, Departments of Engineering Science and Mechanics, Neurosurgery, and Physics, The Pennsylvania State University, University Park, Pennsylvania 16802, United States of America.
Steven J
SJ
Schiff
D001921:Brain / Q000166:cytology* / Q000503:physiopathology*; D048429:Cell Size; D060833:Cellular Microenvironment / Q000502:physiology; D019295:Computational Biology; D003863:Depression / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology* / Q000473:pathology; D012640:Seizures / Q000503:physiopathology*