title: Bioelectric memory: modeling resting potential bistability in amphibian embryos and mammalian cells.
abstract: BACKGROUND
  Bioelectric gradients among all cells, not just within excitable nerve and muscle, play instructive roles in developmental and regenerative pattern formation. Plasma membrane resting potential gradients regulate cell behaviors by regulating downstream transcriptional and epigenetic events. Unlike neurons, which fire rapidly and typically return to the same polarized state, developmental bioelectric signaling involves many cell types stably maintaining various levels of resting potential during morphogenetic events. It is important to begin to quantitatively model the stability of bioelectric states in cells, to understand computation and pattern maintenance during regeneration and remodeling.
  
  
  METHODS
  To facilitate the analysis of endogenous bioelectric signaling and the exploitation of voltage-based cellular controls in synthetic bioengineering applications, we sought to understand the conditions under which somatic cells can stably maintain distinct resting potential values (a type of state memory). Using the Channelpedia ion channel database, we generated an array of amphibian oocyte and mammalian membrane models for voltage evolution. These models were analyzed and searched, by simulation, for a simple dynamical property, multistability, which forms a type of voltage memory.
  
  
  RESULTS
  We find that typical mammalian models and amphibian oocyte models exhibit bistability when expressing different ion channel subsets, with either persistent sodium or inward-rectifying potassium, respectively, playing a facilitative role in bistable memory formation. We illustrate this difference using fast sodium channel dynamics for which a comprehensive theory exists, where the same model exhibits bistability under mammalian conditions but not amphibian conditions. In amphibians, potassium channels from the Kv1.x and Kv2.x families tend to disrupt this bistable memory formation. We also identify some common principles under which physiological memory emerges, which suggest specific strategies for implementing memories in bioengineering contexts.
  
  
  CONCLUSIONS
  Our results reveal conditions under which cells can stably maintain one of several resting voltage potential values. These models suggest testable predictions for experiments in developmental bioelectricity, and illustrate how cells can be used as versatile physiological memory elements in synthetic biology, and unconventional computation contexts.
authors.affiliation: Department of Neuroscience, Brown University, Box G, Providence, RI, 02912, USA. robert_law@brown.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Law
authors.affiliation: Department of Biology and Tufts Center for Regenerative and Developmental Biology, Tufts University, 200 Boston Avenue, Medford, MA, 02155, USA. michael.levin@tufts.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D000663:Amphibians / Q000196:embryology*; D000818:Animals; D002460:Cell Line; D003198:Computer Simulation; D004553:Electric Conductivity; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000502:physiology*; D008322:Mammals; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D015222:Sodium Channels / Q000378:metabolism; D014981:Xenopus
chemical_list: D015222:Sodium Channels