Diverse Current and Voltage Responses to Baclofen in an Identified
Molluscan Photoreceptor.
Matzel, Louis D., Isabel A. Muzzio, & Ronald F. Rogers.
Department of Psychology, Program in Biopsychology and Behavioral
Neuroscience Rutgers University, New Brunswick NJ 08902 USA.
APStracts 2:0120N, 1995.
SUMMARY AND CONCLUSIONS
1. GABA B receptors play a role in the mediation of slow inhibitory
postsynaptic potentials in mammalian as well as some nonmammalian species. In
identified photoreceptors from the marine mollusc Hermissenda , recent
evidence has suggested that GABA, as well as the GABA B receptor agonist
baclofen, might simultaneously modulate multiple conductances on the
postsynaptic membrane. Here, using intracellular voltage and single-electrode
voltage-clamp techniques, we have characterized responses to baclofen in the B
photoreceptors of the Hermissenda eye. 2. Microapplication of baclofen (12.5-
62.5 [mu]M) to the terminal branches of the B photoreceptors induced a slow,
concentration-dependent hyperpolarization ( nearly equal to 3-8 mV) that was
accompanied by a cessation of spontaneous action potentials and a positive
shift in firing threshold. Both the hyperpolarization and the shift in spike
threshold in response to baclofen were largely attenuated by the K + channel
blocker tetraethylammonium chloride (TEA; 50 mM). 3. Bath application of
baclofen (100 [mu]M) decreased the amplitude, duration, and the after-
hyperpolarization (AHP) of evoked action potentials. Although baclofen's
effect on spike duration and amplitude persisted in the absence of
extracellular Ca 2+ , the reduction of the AHP by baclofen was eliminated,
suggesting that multiple conductances mediated the baclofen-induced
modification of the action potential. 4. Using a single-electrode voltage-
clamp technique, microapplication of baclofen to the terminal branches of the
B photoreceptor produced a slow, net outward current (< 0.5 nA) that
reversed near the equilibrium potential for K + and shifted to more positive
potentials when extracellular K + was increased, in approximate agreement with
the Nernst equation for K + . 5. Baclofen induced an increase in amplitude of
the non-voltage dependent leak conductance (I L ), and the increase was
blocked by TEA. The baclofen-induced increase of I L was accompanied by an
increase in amplitude and a negative shift in the voltage dependence of a
slow, steeply voltage-dependent K + current (I K ), which displays selective
sensitivity to TEA but does not normally contribute to leak conductance. The
amplitude and steady-state inactivation of a fast, transient K + current (I A
), as well as the amplitude of an inwardly rectifying K + current (I IR ) were
unaffected by baclofen. 6. Both the rate of activation as well as the
amplitude of a voltage-dependent Ca 2+ current (I ca ) was reduced by
baclofen. The reduction of I Ca resulted in a concomitant suppression of a Ca
2+ -dependent K + current (I K-Ca ) that was sufficient to account for the
reduction of the AHP following evoked action potentials. 7. In total, these
results suggest that the baclofen-induced hyperpolarization and spike
narrowing are attributable to a postsynaptic increase in K + conductance ,
possibly through the I K class channel, while a reduction of the AHP results
from a decrease in I K-Ca that is attributable to a reduction in voltage-
dependent Ca 2+ influx. These responses, as well as the direct reduction of I
Ca by baclofen, are likely to result in a functional decrease in intracellular
Ca 2+ concentration during an action potential, suppressing secretion onto
postsynaptic targets. Thus, GABA B receptors on these neurons may contribute
to both pre- and postsynaptic forms of inhibition.
Received 25 April 1994; accepted in final form 22 March 1995.
APS Manuscript Number J214-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 1 May 1995.