Gastrin-releasing peptide acts via postsynaptic BB2 receptors to modulate inward rectifier K+ and TRPV1-like conductances in rat paraventricular thalamic neurons

Key points center dot Gastrin-releasing peptide (GRP) is a mammalian bombesin-like peptide that is widely distributed in the CNS. Whereas GRP is known to have a predominant excitatory action on neurons, details of the underlying membrane mechanism remain largely undefined. center dot We investigated GRP-affected receptors and ionic conductances in the midline paraventricular thalamic nucleus, a brain region densely innervated by GRP-like immunoreactive fibres. center dot Perforated patch clamp recording in acute brain slices showed that exposure of paraventricular thalamic nucleus neurons to low nanomolar concentrations of GRP resulted in membrane depolarization with rhythmic burst or tonic firing. These responses were due to a postsynaptic bombesin type 2 receptor-mediated simultaneous suppression of a Ba2+-sensitive inward rectifier K+ conductance and activation of a non-selective cation conductance with transient receptor potential vanilloid 1-like properties. center dot The data provide details on the nature of the receptor and ionic conductances involved in GRP's excitatory influence on midline thalamic neurons. Abstract Gastrin-releasing peptide (GRP) is a bombesin-like peptide with a widespread distribution in mammalian CNS, where it has a role in food intake, circadian rhythm generation, fear memory, itch sensation and sexual behaviour. While it has been established that GRP predominantly excites neurons, details of the membrane mechanism involved in this action remain largely undefined. We used perforated patch clamp recording in acute brain slice preparations to investigate GRP-affected receptors and ionic conductances in neurons of the rat paraventricular thalamic nucleus (PVT). PVT is a component of the midline and intralaminar thalamus that participates in arousal, motivational drives and stress responses, and exhibits a prominence of GRP-like immunoreactive fibres. Exposure of PVT neurons to low nanomolar concentrations of GRP induced sustained TTX-resistant membrane depolarizations that could trigger rhythmic burst discharges or tonic firing. Membrane current analyses in voltage clamp revealed an underlying postsynaptic bombesin type 2 receptor-mediated inward current that resulted from the simultaneous suppression of a Ba2+-sensitive inward rectifier K+ conductance and activation of a non-selective cation conductance with biophysical and pharmacological properties reminiscent of transient receptor potential vanilloid (TRPV) 1. A role for a TRPV1-like conductance was further implied by a significant suppressant influence of a TRPV1 antagonist on GRP-induced membrane depolarization and rhythmic burst or tonic firing. The results provide a detailed picture of the receptor and ionic conductances that are involved in GRP's excitatory action in midline thalamus.