Current, voltage and pharmacological substrates of a novel GABA receptor in the visual-vestibular system of Hermissenda

In the marine mollusc, Hermissenda crassicornis, Type B photoreceptors exhibit an IPSP to both presynaptic hair cell stimulation and microapplication of gamma-aminobutyric acid (GABA) to the terminal branches. It was found that both the endogenous IPSP and the response to exogenously applied GABA were mediated to a large part by an outward current which reversed at approximately -80 mV. Additionally, these hyperpolarizing responses were found to mask a smaller depolarization that was mediated by the reduction of a basal outward current. Both the IPSP and the hyperpolarizing response to GABA, as well as the sublimated depolarizing response to GABA, were attenuated by the K+ channel blocker tetraethylammonium chloride (TEA) and displayed a strong sensitivity to [K+]o, while showing no sensitivity to [Cl-]o or the Cl- channel blocker picrotoxin. Moreover, iontophoretic injections of stable guanine analogues, GTP[gamma S] and GDP[beta S], into B photoreceptors eliminated both the IPSP and the GABA-induced hyperpolarization, while cholinergically mediated, interphotoreceptor interactions were unaffected. These results suggest that the endogenous receptor is at least partially homologous to the mammalian GABAB class receptor. Consistent with this classification, microapplication of selective GABAB receptor agonist baclofen onto the terminal region of the B photoreceptor resulted in a hyperpolarizing response that was qualitatively similar to that of GABA, although the GABAA agonist muscimol was also active, but less so than either GABA or baclofen. Attempts to block the endogenous IPSP or GABA-induced hyperpolarization by bath application of the GABAA receptor subtype antagonist bicuculline was ineffective and the GABAB receptor subtype antagonist saclofen was only weakly effective. These data demonstrate that the presynaptic hair cell's influence on postsynaptic B photoreceptors is in many respects similar to GABAB mediated responses in the mammalian CNS. This receptor is in some respects unique, however, in terms of its cross-sensitivity to both GABAA and GABAB agonists, its weak sensitivity to saclofen, and its apparent anomalous modulation of multiple K+ conductances.

[1]  D. Carpenter,et al.  Receptors for gamma-aminobutyric acid (GABA) on aplysia neurons , 1978, Brain Research.

[2]  P. Gage.  Activation and modulation of neuronal K+ channels by GABA , 1992, Trends in Neurosciences.

[3]  K. Oka,et al.  Long-term transformation of an inhibitory into an excitatory GABAergic synaptic response. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[4]  K. Ikeda,et al.  Dose-conductance relationships for GABA agonists and the effect of uptake inhibitors in crayfish stretch receptor neurons , 1981, Brain Research.

[5]  R. Moratalla,et al.  Regional effects of pertussis toxin in vivo and in vitro on GABAB receptor binding in rat brain , 1993, Neuroscience.

[6]  Grigori N. Orlovsky,et al.  Pharmacologically induced elements of the hunting and feeding behavior in the pteropod mollusk Clione limacina. I: Effects of GABA , 1993 .

[7]  R. Nicoll,et al.  A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. , 1986, Science.

[8]  N. Harrison.  On the presynaptic action of baclofen at inhibitory synapses between cultured rat hippocampal neurones. , 1990, The Journal of physiology.

[9]  S. Siegelbaum,et al.  Role of two different guanine nucleotide-binding proteins in the antagonistic modulation of the S-type K+ channel by cAMP and arachidonic acid metabolites in Aplysia sensory neurons. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Dolphin,et al.  Calcium channel currents and their inhibition by (‐)‐baclofen in rat sensory neurones: modulation by guanine nucleotides. , 1987, The Journal of physiology.

[11]  J Farley.  Contingency learning and causal detection in Hermissenda: II. Cellular mechanisms. , 1987, Behavioral neuroscience.

[12]  D. Alkon,et al.  GABA‐Mediated Synaptic Interaction Between the Visual and Vestibular Pathways of Hermissenda , 1993, Journal of neurochemistry.

[13]  Makoto Sato,et al.  A single GTP-binding protein regulates K+-channels coupled with dopamine, histamine and acetylcholine receptors , 1987, Nature.

[14]  S. Siegelbaum,et al.  Antagonistic Modulation of S‐K+ Channel Activity by Cyclic AMP and Arachidonic Acid Metabolites Role for Two G Proteins a , 1989, Annals of the New York Academy of Sciences.

[15]  P. Fossier,et al.  G proteins are involved in the regulation of transmitter release at an Aplysia cholinergic synapse , 1992, Brain Research.

[16]  T. Crow.  Cellular and molecular analysis of associative learning and memory in Hermissenda , 1988, Trends in Neurosciences.

[17]  L. Matzel,et al.  Postsynaptic calcium, but not cumulative depolarization, is necessary for the induction of associative plasticity in Hermissenda , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  Joseph Farley,et al.  Serotonin modulation ofHermissenda type B photoreceptor light responses and ionic currents: Implications for mechanisms underlying associative learning , 1989, Brain Research Bulletin.

[19]  A. Gilman,et al.  G proteins: transducers of receptor-generated signals. , 1987, Annual review of biochemistry.

[20]  K. Wann,et al.  The action of GABA receptor agonists and antagonists on muscle membrane conductance in Schistocerca gregaria , 1988, British journal of pharmacology.

[21]  K. Oka,et al.  The role of calcium in prolonged modification of a GABAergic synapse , 1992, Journal of Physiology-Paris.

[22]  R. Nicoll,et al.  Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells , 1984, Nature.

[23]  T. Crow,et al.  Serotonin modulates photoresponses in Hermissenda type-B photoreceptors , 1985, Neuroscience Letters.

[24]  E. Philippe,et al.  Baclofen modifies via the release of monoamines the synaptic depression, frequency facilitation, and posttetanic potentiation observed at an identified cholinergic synapse of Aplysia californica. , 1981, Canadian journal of physiology and pharmacology.

[25]  D. Alkon,et al.  Neurotransmitter synthesis in the nervous system of the mollusc Hermissenda. , 1978, Comparative biochemistry and physiology. C: Comparative pharmacology.

[26]  H. Takeuchi,et al.  Pharmacological characteristics of two different types of inhibitory GABA receptors on Achatina fulica neurones. , 1990, European journal of pharmacology.

[27]  D L Alkon,et al.  Voltage-dependent calcium and calcium-activated potassium currents of a molluscan photoreceptor. , 1984, Biophysical journal.

[28]  R. Walker,et al.  The ionic mechanism associated with the action of putative transmitters on identified neurons of the snail, Helix aspersa. , 1986, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[29]  N. Akaike,et al.  GABA and lioresal actions on the identified Onchidium neuron. , 1983, The Japanese journal of physiology.

[30]  F. Clarac,et al.  GABA‐Mediated Presynaptic Inhibition in Crayfish Primary Afferents by Non‐A, Non‐B GABA Receptors , 1991, The European journal of neuroscience.

[31]  D. Carpenter,et al.  Voltage-clamp characterization of Cl- conductance gated by GABA and L-glutamate in single neurons of Aplysia. , 1989, Journal of Neurophysiology.

[32]  David E. Clapham,et al.  Roles of G protein subunits in transmembrane signalling , 1988, Nature.

[33]  R. Nicoll,et al.  Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties , 1988, Neuron.

[34]  J. Bormann.  Electrophysiology of GABAA and GABAB receptor subtypes , 1988, Trends in Neurosciences.

[35]  D. Sattelle,et al.  Pharmacological and biochemical properties of insect GABA receptors. , 1990, Trends in pharmacological sciences.

[36]  R. Walker.  Transmitters and Modulators , 1986 .

[37]  F. Franciolini,et al.  Chloride channels of biological membranes. , 1990, Biochimica et biophysica acta.

[38]  B. Hue,et al.  Presynaptic inhibition in the cercal-afferent giant-interneurone synapses of the cockroach, Periplaneta americana L. , 1983 .

[39]  D. Alkon,et al.  GABA-induced potentiation of neuronal excitability occurs during contiguous pairings with intracellular calcium elevation , 1991, Brain Research.

[40]  D. Alkon,et al.  Associative Behavioral Modification in Hermissenda: Cellular Correlates , 1980, Science.

[41]  Intersensory Interactions in Hermissenda , 1973, The Journal of general physiology.

[42]  GABAB receptors expressed in Xenopus oocytes by guinea pig cerebral mRNA are functionally coupled with Ca2(+)-dependent Cl- channels and with K+ channels, through GTP-binding proteins. , 1990, Brain research. Molecular brain research.

[43]  W. Wisden,et al.  Function and pharmacology of multiple GABAA receptor subunits. , 1991, Trends in pharmacological sciences.

[44]  D. Kerr,et al.  2-Hydroxy-saclofen: an improved antagonist at central and peripheral GABAB receptors , 1988, Neuroscience Letters.