title: GABA and glutamate receptors have different effects on excitability and are differentially regulated by calcium in spider mechanosensory neurons.
abstract: GABA and glutamate receptors belonging to the ligand-gated chloride-channel family are primary targets of insecticides and antiparasitics, so their molecular structure, pharmacology and biophysical properties have attracted significant attention. However, little is known about the physiological roles of these channels or how they regulate neuronal excitability and animal behavior. Mechanosensory neurons of VS-3 slit sensilla in the patella of the tropical wandering spider, Cupiennius salei, react to the GABA(A)-receptor agonists, GABA and muscimol, with depolarization and an increase in intracellular [Ca(2+)] and, during random noise stimulation, with a mixed inhibitory-excitatory response. We established that the GABA(A)-receptors in all VS-3 neurons are identical, but there are at least two types of glutamate receptors and some neurons do not respond to glutamate at all. Immunohistochemistry with antibodies against Drosophila inhibitory glutamate receptor (GluCls) α-subunit suggests that in addition to VS-3 neurons, these receptors may also be present in the efferent neurons surrounding the sensory neurons. Most VS-3 neurons were inhibited but not depolarized by glutamate during random stimulation, but some depolarized and had a similar excitatory-inhibitory response to glutamate as to muscimol. The membrane-permeable Ca(2+)-chelator BAPTA-AM abolished muscimol effects but potentiated glutamate effects, indicating that GABA and glutamate receptors are differentially modulated by Ca(2+), leading to diverse regulation of neuronal excitability. We hypothesize that this could be achieved by different Ca(2+)-triggered phosphorylation processes at each receptor type. These findings are important for understanding the significance of Ca(2+)-mediated regulation of transmitter receptor molecules and its role in controlling excitability.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, PO Box 15000, Halifax, NS, B3H 4R2, Canada. paivi.torkkeli@dal.ca
authors.forename: Päivi H
authors.initials: PH
authors.lastname: Torkkeli
authors.forename: Shannon
authors.initials: S
authors.lastname: Meisner
authors.forename: Keram
authors.initials: K
authors.lastname: Pfeiffer
authors.forename: Andrew S
authors.initials: AS
authors.lastname: French
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D019476:Insect Proteins / Q000378:metabolism*; D008465:Mechanoreceptors / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials; D009118:Muscimol / Q000494:pharmacology; D009476:Neurons, Efferent / Q000378:metabolism; D010766:Phosphorylation; D011963:Receptors, GABA-A / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D058618:Sensilla / Q000502:physiology; D013112:Spiders; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D058785:GABA-A Receptor Agonists; D019476:Insect Proteins; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium