Activation of postsynaptic GABAB receptors modulate the firing activity of supraoptic oxytocin and vasopressin neurones: role of calcium channels.
Oxytocin and vasopressin release from neurohypophysial terminals is closely related to the firing activity of magnocellular neurones in the supraoptic (SON) and paraventricular nuclei. It is well established that activation of GABAA receptors potently inhibits the activity of SON neurones and, thus, hormone release. However, whether postsynaptic GABAB receptors are expressed in magnocellular neurones, and the role they play in controlling their firing activity, is still controversial. In the present work, we combined immunohistochemical and electrophysiological techniques to determine whether activation of GABAB receptors in identified oxytocin and vasopressin neurones modulates their firing activity. Patch-clamp recordings from SON neurones were obtained either in the slice preparation or from acutely dissociated neurones. Activation of GABAB receptors with the selective agonist baclofen (10 micro m) inhibited voltage-gated Ca2+ currents, reduced the duration of individual action potentials, as well as the magnitude of the hyperpolarizing after-potential. SON firing activity was reduced by baclofen, and effect that was accompanied by a small membrane hyperpolarization. The inhibition of firing discharge persisted in the presence of synaptic blockade media, and was also observed in acutely dissociated SON neurones. Finally, GABAB-mediated modulation of firing activity was largely blocked by the Ca2+ channel blocker Co2+ (2 mm). In general, baclofen modulatory actions were significantly larger, or observed more predominantly, in vasopressin neurones. In summary, these results support the expression of functional postsynaptic GABAB receptors in SON neurones, activation of which efficiently modulates neuronal excitability, in a Ca2+- and cell-type dependent manner.
Li
Y
Y
Department of Pharmacology and Toxicology, Wright State University, Dayton, OH 45435, USA.
Stern
J E
JE
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D007150:Immunohistochemistry; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000378:metabolism*; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018755:GABA Agonists; D018080:Receptors, GABA-B; D014667:Vasopressins; D003035:Cobalt; D010121:Oxytocin; D001418:Baclofen