title: Competitive calcium binding: implications for dendritic calcium signaling.
abstract: Action potentials evoke calcium transients in dendrites of neocortical pyramidal neurons with time constants of < 100 ms at physiological temperature. This time period may not be sufficient for inflowing calcium ions to equilibrate with all present Ca2+-binding molecules. We therefore explored nonequilibrium dynamics of Ca2+ binding to numerous Ca2+ reaction partners within a dendritelike compartment using numerical simulations. After a brief Ca2+ influx, the reaction partner with the fastest Ca2+ binding kinetics initially binds more Ca2+ than predicted from chemical equilibrium, while companion reaction partners bind less. This difference is consolidated and may result in bypassing of slow reaction partners if a Ca2+ clearance mechanism is active. On the other hand, slower reaction partners effectively bind Ca2+ during repetitive calcium current pulses or during slower Ca2+ influx. Nonequilibrium Ca2+ distribution can further be enhanced through strategic placement of the reaction partners within the compartment. Using the Ca2+ buffer EGTA as a competitor of fluo-3, we demonstrate competitive Ca2+ binding within dendrites experimentally. Nonequilibrium calcium dynamics is proposed as a potential mechanism for differential and conditional activation of intradendritic targets.
authors.affiliation: Department of Neurobiology, Weizmann Institute, Rehovot, Israel. bnmark@weizmann.weizmann.ac.il
authors.forename: H
authors.initials: H
authors.lastname: Markram
authors.forename: A
authors.initials: A
authors.lastname: Roth
authors.forename: F
authors.initials: F
authors.lastname: Helmchen
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003712:Dendrites / Q000737:chemistry / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007700:Kinetics; D008959:Models, Neurological; D019579:Neocortex / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D002614:Chelating Agents; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium