Dual modulation of inward rectifier potassium currents in olfactory neuronal cells by promiscuous G protein coupling of the oxytocin receptor.
Oxytocin receptor is a seven transmembrane receptor widely expressed in the CNS that triggers G(i) or G(q) protein-mediated signaling cascades leading to the regulation of a variety of neuroendocrine and cognitive functions. We decided to investigate whether and how the promiscuous receptor/G protein coupling affects neuronal excitability. As an experimental model, we used the immortalized gonadotropin-releasing hormone-positive GN11 cell line displaying the features of immature, migrating olfactory neurons. Using RT-PCR analysis, we detected the presence of oxytocin receptors whose stimulation by oxytocin led to the accumulation of inositol phosphates and to the inhibition of cell proliferation, and the expression of several inward rectifier (IR) K+ channel subtypes. Moreover, electrophysiological and pharmacological inspections using whole-cell patch-clamp recordings evidenced that in GN11 cells, IR channel subtypes are responsive to oxytocin. In particular, we found that: (i) peptide activation of receptor either inhibited or stimulated IR conductances, and (ii) IR current inhibition was mediated by a pertussis toxin-resistant G protein presumably of the G(q/11) subtype, and by phospholipase C, whereas IR current activation was achieved via receptor coupling to a pertussis toxin-sensitive G(i/o) protein. The findings suggest that neuronal excitability might be tuned by a single peptide receptor that mediates opposing effects on distinct K+ channels through the promiscuous coupling to different G proteins.
Gravati
Marta
M
Department of Physiology, University of Pavia, Pavia, Italy.
Busnelli
Marta
M
Bulgheroni
Elisabetta
E
Reversi
Alessandra
A
Spaiardi
Paolo
P
Parenti
Marco
M
Toselli
Mauro
M
Chini
Bice
B
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010121:Oxytocin / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000819:agonists / Q000378:metabolism / Q000502:physiology*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018045:Receptors, Oxytocin; D010121:Oxytocin