title: Simulation in sensory neurons reveals a key role for delayed Na+ current in subthreshold oscillations and ectopic discharge: implications for neuropathic pain.
abstract: Somata of primary sensory neurons are thought to contribute to the ectopic neural discharge that is implicated as a cause of some forms of neuropathic pain. Spiking is triggered by subthreshold membrane potential oscillations that reach threshold. Oscillations, in turn, appear to result from reciprocation of a fast active tetrodotoxin-sensitive Na+ current (INa+) and a passive outward IK+ current. We previously simulated oscillatory behavior using a transient Hodgkin-Huxley-type voltage-dependent INa+ and ohmic leak. This model, however, diverged from oscillatory parameters seen in live cells and failed to produce characteristic ectopic discharge patterns. Here we show that use of a more complete set of Na+ conductances--which includes several delayed components--enables simulation of the entire repertoire of oscillation-triggered electrogenic phenomena seen in live dorsal root ganglion (DRG) neurons. This includes a physiological window of induction and natural patterns of spike discharge. An INa+ component at 2-20 ms was particularly important, even though it represented only a tiny fraction of overall INa+ amplitude. With the addition of a delayed rectifier IK+ the singlet firing seen in some DRG neurons can also be simulated. The model reveals the key conductances that underlie afferent ectopia, conductances that are potentially attractive targets in the search for more effective treatments of neuropathic pain.
authors: Department of Cell and Developmental Biology, Institute of Life Sciences, Center for Research on Pain, Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
authors: Yifat
authors: Y
authors: Kovalsky
authors: Ron
authors: R
authors: Amir
authors: Marshall
authors: M
authors: Devor
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D003198:Computer Simulation; D004558:Electric Stimulation / Q000379:methods; D015640:Ion Channel Gating / Q000502:physiology; D008959:Models, Neurological; D009431:Neural Conduction / Q000502:physiology; D009433:Neural Inhibition; D011984:Sensory Receptor Cells / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D015222:Sodium Channels