title: Computational study of enhanced excitability in Hermissenda: membrane conductances modulated by 5-HT.
abstract: Serotonin (5-HT) applied to the exposed but otherwise intact nervous system results in enhanced excitability of Hermissenda type-B photoreceptors. Several ion currents in the type-B photoreceptors are modulated by 5-HT, including the A-type K+ current (I(K,A)), sustained Ca2+ current (I(Ca,S)), Ca-dependent K+ current (I(K,Ca)), and a hyperpolarization-activated inward rectifier current (I(h)). In this study, we developed a computational model that reproduces physiological characteristics of type B photoreceptors, e.g. resting membrane potential, dark-adapted spike activity, spike width, and the amplitude difference between somatic and axonal spikes. We then used the model to investigate the contribution of different ion currents modulated by 5-HT to the magnitudes of enhanced excitability produced by 5-HT. Ion currents were systematically varied within limits observed experimentally, both individually and in combinations. A reduction of I(K,A) or I(K,Ca), or an increase in I(h) enhanced excitability by 20-50%. Decreasing I(Ca,S) produced a dramatic decrease in excitability. Reductions of I(K,V) produced only minimal increases in excitability, suggesting that I(K,V) probably plays a minor role in 5-HT induced enhanced excitability. Combinations of changes in I(K,A), I(K,Ca), I(h) and I(Ca,S) produced increases in excitability comparable to experimental observations. After 5-HT application, the cell's depolarization force is shifted from the I(h)-I(Ca,S) combination to predominantly I(h).
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas at Houston Medical School, Houston, Texas 77030, USA. yidao.cai@uth.tmc.edu
authors.forename: Yidao
authors.initials: Y
authors.lastname: Cai
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Baxter
authors.forename: Terry
authors.initials: T
authors.lastname: Crow
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D003198:Computer Simulation; D051668:Delayed Rectifier Potassium Channels; D006801:Humans; D008433:Mathematics; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D008974:Mollusca / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011930:Reaction Time; D012701:Serotonin / Q000378:metabolism*
chemical_list: D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012701:Serotonin