title: GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord.
abstract: Activation of GABAB receptors in the Xenopus embryo, a simple vertebrate, causes presynaptic inhibition of transmitter release from glycinergic spinal neurons and an increase in action potential threshold. To investigate the underlying mechanisms of GABAB receptor action, we have made whole-cell voltage-clamp recordings from acutely isolated Xenopus embryo spinal neurons. The GABAB receptor agonist baclofen caused a reversible reduction in the amplitude of Ca2+ currents. This reduction of Ca2+ currents appeared to be voltage dependent as it was removed at very positive potentials. Since the specific GABAB antagonists CGP35348, phaclofen, and 2-hydroxysaclofen all blocked the reduction in Ca2+ currents, we concluded that the modulation of the Ca2+ current was mediated by GABAB receptors. We have investigated the pharmacological identity of the Ca2+ current modulated by baclofen using the selective blocker omega-conotoxin, fraction GVIA (omega-CgTX). omega-CgTX selectively blocked voltage-gated Ca2+ currents without affecting the voltage-gated Na+ current. omega-CgTX substantially occluded the action of baclofen, suggesting that GABAB receptors modulate an omega-CgTX-sensitive Ca2+ current. Since GABAB receptors mediate presynaptic inhibition, we have studied the involvement of the omega-CgTX-sensitive Ca2+ current in synaptic transmission in the intact spinal cord. Inhibitory interneuron axons were stimulated to evoke monosynaptic IPSPs in motoneurons, and recorded intracellularly. Since omega-CgTX blocked inhibitory transmission, we concluded that the omega-CgTX-sensitive Ca2+ current plays an essential role in transmitter release. If modulation of this current were to occur in nerve terminals, it could contribute to the GABAB receptor-mediated presynaptic inhibition of transmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: School of Biological Sciences, Bristol University, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Wall
authors.forename: N
authors.initials: N
authors.lastname: Dale
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D018079:Receptors, GABA / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus / Q000196:embryology*; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018756:GABA Antagonists; D010455:Peptides; D015221:Potassium Channels; D018079:Receptors, GABA; D020866:omega-Conotoxin GVIA; D001418:Baclofen; D002118:Calcium