title: Overexpression of a hyperpolarization-activated cation current (Ih) channel gene modifies the firing activity of identified motor neurons in a small neural network.
abstract: The hyperpolarization-activated cation current (Ih) is widely distributed in excitable cells. Ih plays important roles in regulation of cellular excitability, rhythmic activity, and synaptic function. We previously showed that, in pyloric dilator (PD) neurons of the stomatogastric ganglion (STG) of spiny lobsters, Ih can be endogenously upregulated to compensate for artificial overexpression of the Shal transient potassium channel; this maintains normal firing properties of the neuron despite large increases in potassium current. To further explore the function of Ih in the pyloric network, we injected cRNA of PAIH, a lobster gene that encodes Ih, into rhythmically active PD neurons. Overexpression of PAIH produced a fourfold increase in Ih, although with somewhat different biophysical properties than the endogenous current. Compared with the endogenous Ih, the voltage for half-maximal activation of the PAIH-evoked current was depolarized by 10 mV, and its activation kinetics were significantly faster. This increase in Ih did not affect the expression of IA or other outward currents. Instead, it significantly altered the firing properties of the PD neurons. Increased Ih depolarized the minimum membrane potential of the cell, reduced the oscillation amplitude, decreased the time to the first spike, and increased the duty cycle and number of action potentials per burst. We used both dynamic-clamp experiments, injecting the modeled PAIH currents into PD cells in a functioning STG, and a theoretical model of a two-cell network to demonstrate that the increased Ih was sufficient to cause the observed changes in the PD activity.
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, USA. yz34@cornell.edu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ricardo
authors.initials: R
authors.lastname: Oliva
authors.forename: Günter
authors.initials: G
authors.lastname: Gisselmann
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.forename: John
authors.initials: J
authors.lastname: Guckenheimer
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Harris-Warrick
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003198:Computer Simulation; D054815:Cyclic Nucleotide-Gated Cation Channels; D005456:Fluorescent Dyes; D017952:Ganglia, Invertebrate / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D033521:Palinuridae / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D015221:Potassium Channels; D018075:RNA, Complementary / Q000235:genetics / Q000494:pharmacology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D005456:Fluorescent Dyes; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D018075:RNA, Complementary