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This Article Full Text Full Text (PDF) All Versions of this Article: 551/1/295    most recent jphysiol.2003.041319v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Slugg, R. M. Articles by Rønnekleiv, O. K. Search for Related Content PubMed PubMed Citation Articles by Slugg, R. M. Articles by Rønnekleiv, O. K.

Baclofen inhibits guinea pig magnocellular neurones via activation of an inwardly rectifying K⁺ conductance

Robert M. Slugg*, Shi-Xi Zheng*, Yuan Fang*, Martin J. Kelly*† and Oline K. Rønnekleiv*†

The GABA_B receptors GABA_B-R1 and GABA_B-R2 have been cloned in several mammalian species, and the functional receptor has been shown to exist as a heterodimeric complex. We have cloned guinea pig GABA_B-R1 and GABA_B-R2 receptor sequences and, using in situ hybridization and immunocytochemistry for vasopressin (AVP), we found that GABA_B-R1 and -R2 receptors are expressed in vasopressin neurones of the supraoptic (SON) and paraventricular nuclei (PVN). Therefore, we used both sharp electrode and whole-cell patch recording techniques to examine the effects of the selective GABA_B agonist baclofen on SON and PVN magnocellular neurones and to determine the coupling of the GABA_B receptor to effector pathways. Recordings were made in coronal hypothalamic slices from both female (ovariectomized) and male guinea pigs. In the presence of tetrodotoxin (TTX), baclofen hyperpolarized (V_max = 5.6 mV, EC₅₀ = 2.3 µM) SON magnocellular neurones (n = 27) under current clamp, or induced an outward current that reversed at E_K (I_max = 24.2 pA) in PVN magnocellular neurones (n = 33) under voltage clamp. Seventeen of the 24 biocytin-labelled SON magnocellular neurones were identified as AVP neurones, and ten of the 33 biocytin-labelled PVN neurones were identified as AVP or neurophysin-containing neurones, although all of the cells were clustered in the vasopressin-rich core. In the absence of TTX, baclofen activated an outward K⁺ current that hyperpolarized SON and PVN neurones and significantly reduced their firing rate. The outward current showed inward rectification and was blocked by the K⁺ channel blocker barium and the GABA_B receptor antagonist CGP 35348. Therefore, GABA_B receptors are coupled to inwardly rectifying K⁺ channels in SON and PVN magnocellular neurones and may play a prominent role in modulating phasic bursting activity in guinea pig vasopressin neurones.

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