[Abstract Title]. - Society for Neuroscience

Topic: D.09.b. Receptors
Support: CIHR
NSHRF
Title: Mechanisms of GABAA receptor mediated excitation of spider mechanosensory neurons
Authors: K. PFEIFFER, U. HOEGER, A. S. FRENCH, *P. H. TORKKELI;
Dept Physiol & Biophys, Dalhousie Univ., Halifax, NS, Canada
Abstract: Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter. In
mechanosensory afferents entering the vertebrate spinal cord, and arthropod central ganglia,
activation of ionotropic GABAA receptors causes inhibition via primary afferent depolarization
and increased membrane conductance (shunting). Similar inhibition by depolarization and
shunting occurs in mechanosensory neurons of VS-3 slit-sense organ of the spider (Cupiennius
salei) when the GABAA receptor agonists GABA or muscimol are applied while the neurons are
stimulated with mechanical or electrical step stimuli.
Here we found that when the VS-3 neurons were stimulated with more natural stimuli of varying
amplitude and frequency (pseudorandom noise) during muscimol application, the initial
inhibition was followed by excitation lasting up to ten minutes. Frequency response analysis
during this excitation, followed by power law fitting, indicated that the firing rate, sensitivity,
adaptation (fractional exponent) and information capacity all increased significantly.
Using voltage clamp controlled current clamp (VCcCC), which allows action potential recording
while mean membrane potential is clamped to a desired value, we tested whether depolarization
of VS-3 neurons alone would be sufficient to elicit the excitatory response. Depolarization by
10-20 mV during mechanical noise stimulation caused significant increases in the firing rate and
information capacity, while sensitivity and fractional exponent did not change. However, when
neurons were clamped to the resting potential during muscimol application, firing rate,
sensitivity and information capacity increased significantly, while fractional exponent was not
affected.
Muscimol increases intracellular Ca 2+ concentration in VS-3 neurons by opening low-voltageactivated
Ca 2+ channels during depolarization (Panek et al. 2008, J Neurophysiol 99:1596-1606).
To learn if the excitatory muscimol response depended on Ca 2+ influx, we blocked Ca 2+ channels
with 100 µM Ni 2+ . In most experiments this led to a 50% reduction in the muscimol-induced
increase in sensitivity, without significant changes in the fractional exponent or information
capacity.
Our results show that when spider VS-3 neurons were stimulated with randomly varying signals,
the initial inhibitory response to GABAA receptor activation was followed by a long lasting
excitation. This excitation may be partially mediated by Ca 2+ influx during depolarization.
However, it also occurred when the neurons were clamped at their resting potential, suggesting
that additional mechanisms are probably involved.
Disclosures: K. Pfeiffer, None; U. Hoeger, None; A.S. French, None; P.H. Torkkeli , None.