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Title: | Frequency-dependent modulation of glycine receptor activation recorded from the zebrafish larvae hindbrain | Authors: | RIGO, Jean-Michel Legendre, P |
Issue Date: | 2006 | Source: | Neuroscience, 140(2). p. 389-402 | Abstract: | In vertebrates, most glycinergic inhibitory neurons discharge phasically at a relatively low frequency. Such a pattern of glycine liberation from presynaptic terminals may affect the kinetics of post-synaptic glycine receptors. To examine this influence, we have analyzed the behavior of glycine receptors in response to repetitive stimulation at frequencies at which consecutive outside-out currents did not superimpose (0.5-4 Hz). Neurotransmitter release was mimicked on outside-out patches from zebrafish hindbrain Mauthner cells using fast flow application techniques. The amplitude of outside-out currents evoked by short (1 ms) repetitive applications of a saturating concentration (3 mM) of glycine remained unchanged for application frequencies :51 Hz. When the application frequency was increased from 1 to 4 Hz, the amplitude of the outside-out currents decreased with time to reach a steady state level. This decrease in current amplitude was larger and occurred faster with increasing application frequencies. Recovery occurred when the stimulation frequency was decreased back to 1 Hz. The recovery time constant was independent on the application frequency. This frequency-dependent inhibition was also observed for non-saturating glycine concentrations. Our results indicate that glycine receptor activity is down-regulated when the stimulation frequency increases to values > 1 Hz. Glycine-evoked current simulations using a simple Markov model describing zebrafish glycine receptor kinetic behavior, indicates that this down-regulation of glycine receptor efficacy is due to a progressive accumulation of the receptors in a long lasting desensitization state. Our simulations suggest that this down-regulation can occur even when spontaneous inhibitory currents were generated randomly at a frequency > 1 Hz. (c) 2006 Published by Elsevier Ltd on behalf of IBRO. | Keywords: | glycine receptors; patch-clamp; desensitization; frequency; synaptic; activity; modulation; RAT HYPOGLOSSAL MOTONEURONS; KINETIC-ANALYSIS; BETA-SUBUNIT; TIME-COURSE; IN-VITRO; CURRENTS; NEURONS; CHANNELS; NUCLEUS; RELEASE | Document URI: | http://hdl.handle.net/1942/1402 | ISSN: | 0306-4522 | e-ISSN: | 1873-7544 | DOI: | 10.1016/j.neuroscience.2006.01.057 | ISI #: | 000237902400002 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2007 |
Appears in Collections: | Research publications |
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