title: Random stimulation of spider mechanosensory neurons reveals long-lasting excitation by GABA and muscimol.
abstract: gamma-Aminobutyric acid type A (GABA(A)) receptor activation inhibits many primary afferent neurons by depolarization and increased membrane conductance. Deterministic (step and sinusoidal) functions are commonly used as stimuli to test such inhibition. We found that when the VS-3 mechanosensory neurons innervating the spider lyriform slit-sense organ were stimulated by randomly varying white-noise mechanical or electrical signals, their responses to GABA(A) receptor agonists were more complex than the inhibition observed during deterministic stimulation. Instead, there was rapid excitation, then brief inhibition, followed by long-lasting excitation. During the final excitatory phase, VS-3 neuron sensitivity to high-frequency signals increased selectively and their linear information capacity also increased. Using experimental and simulation approaches we found that the excitatory effect could also be achieved by depolarizing the neurons without GABA application and that excitation could override the inhibitory effect produced by increased membrane conductance (shunting). When the VS-3 neurons were exposed to bumetanide, an antagonist of the Cl(-) transporter NKCC1, the GABA-induced depolarization decreased without any change in firing rate, suggesting that the effects of GABA can be maintained for a long time without additional Cl(-) influx. Our results show that the VS-3 neuron's response to GABA depends profoundly on the type of signals the neuron is conveying while the transmitter binds to its receptors.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5.
authors.forename: Keram
authors.initials: K
authors.lastname: Pfeiffer
authors.forename: Izabela
authors.initials: I
authors.lastname: Panek
authors.forename: Ulli
authors.initials: U
authors.lastname: Höger
authors.forename: Andrew S
authors.initials: AS
authors.lastname: French
authors.forename: Päivi H
authors.initials: PH
authors.lastname: Torkkeli
mesh_terms: D000465:Algorithms; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004558:Electric Stimulation; D005665:Furosemide / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D040542:Mechanotransduction, Cellular / Q000187:drug effects* / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology*; D013112:Spiders / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D002712:Chlorides; D004232:Diuretics; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D002034:Bumetanide; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005665:Furosemide