title: GABA(B)-mediated inhibition of multiple modes of glutamate release in the nucleus of the solitary tract.
abstract: In the caudal portions of the solitary tract (ST) nucleus, primary sensory afferents fall into two broad classes based on the expression of transient receptor potential vanilloid type 1 (TRPV1) receptors. Both afferent classes (TRPV1+/-) have indistinguishable glutamate release mechanisms for ST-evoked excitatory postsynaptic currents (EPSCs). However, TRPV1+ terminals release additional glutamate from a unique, TRPV1-operated vesicle pool that is temperature sensitive and facilitated by ST activity to generate asynchronous EPSCs. This study tested whether presynaptic γ-aminobutyric acid (GABA)(B) receptors inhibit both the evoked and TRPV1-operated release mechanisms on second-order ST nucleus neurons. In horizontal slices, shocks activated single ST axons and evoked the time-invariant (latency jitter <200 μs), glutamatergic EPSCs, which identified second-order neurons. Gabazine eliminated GABA(A) responses in all recordings. The GABA(B) agonist baclofen inhibited the amplitude of ST-EPSCs from both TRPV1+ and TRPV1- afferents with a similar EC(50) (∼1.2 μM). In TTX, GABA(B) activation decreased miniature EPSC (mEPSC) rates but not amplitudes, suggesting presynaptic actions downstream from terminal excitability. With calcium entry through voltage-activated calcium channels blocked by cadmium, baclofen reduced mEPSC frequency, indicating that GABA(B) reduced vesicle release by TRPV1-dependent calcium entry. GABA(B) activation also reduced temperature-evoked increases in mEPSC frequency, which relies on TRPV1. Our studies indicate that GABA(B) G protein-coupled receptors are uniformly distributed across all ST primary afferent terminals and act at multiple stages of the excitation-release cascades to suppress both action potential-triggered and TRPV1-coupled glutamate transmission pathways. Moreover, the segregated release cascades within TRPV1+ ST primary afferents represent independent, potential targets for differential modulation.
authors: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, USA. fawley.jessica@gmail.com
authors: Jessica A
authors: JA
authors: Fawley
authors: James H
authors: JH
authors: Peters
authors: Michael C
authors: MC
authors: Andresen
mesh_terms: D000200:Action Potentials; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000145:classification / Q000502:physiology*
chemical_list: D001596:Benzylamines; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C083008:CGP 52432; D018698:Glutamic Acid; D001418:Baclofen