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  • Title: Baclofen inhibits guinea pig magnocellular neurones via activation of an inwardly rectifying K+ conductance.
    Author: Slugg RM, Zheng SX, Fang Y, Kelly MJ, Rønnekleiv OK.
    Journal: J Physiol; 2003 Aug 15; 551(Pt 1):295-308. PubMed ID: 12813153.
    Abstract:
    The GABAB receptors GABAB-R1 and GABAB-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 GABAB-R1 and GABAB-R2 receptor sequences and, using in situ hybridization and immunocytochemistry for vasopressin (AVP), we found that GABAB-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 GABAB agonist baclofen on SON and PVN magnocellular neurones and to determine the coupling of the GABAB 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 (DeltaVmax = 5.6 mV, EC50 = 2.3 microM) SON magnocellular neurones (n = 27) under current clamp, or induced an outward current that reversed at EK (DeltaImax = 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 GABAB receptor antagonist CGP 35348. Therefore, GABAB 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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