These authors contributed equally to this work.
Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
Article first published online: 12 JUN 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 126, Issue 6, pages 705–714, September 2013
How to Cite
J. Neurochem. (2013) 126, 705–714.
- Issue published online: 6 SEP 2013
- Article first published online: 12 JUN 2013
- Accepted manuscript online: 20 MAY 2013 11:37AM EST
- Manuscript Accepted: 15 MAY 2013
- Manuscript Revised: 14 MAY 2013
- Manuscript Received: 8 APR 2013
- NIH. Grant Number: F31 HL10842
- Center for Translational Neuroscience. Grant Number: P20 GM103425
- Agencia Nacional de Promoción Científica y Tecnológica. Grant Number: P20 GM103425
- GDPβ, GTPγS;
- hyperpolarization-activated cation current;
- sodium current
The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G-protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole-cell patch clamp recordings were performed in rat brainstem slices from 9 to 17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (INa) and h-current (IH) in PPN neurons. TA (100 nM) reduced the blockade of INa (~ 50% reduction) and IH (~ 93% reduction) caused by leptin. Intracellular guanosine 5′-[β-thio]diphosphate trilithium salt (a G-protein inhibitor) significantly reduced the effect of leptin on INa(~ 60% reduction) but not on IH (~ 25% reduction). Intracellular GTPγS (a G-protein activator) reduced the effect of leptin on both INa (~ 80% reduction) and IH (~ 90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor- and G-protein dependent. We also found that leptin enhanced NMDA receptor-mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances.
Beck et al. investigated the effects of leptin on the intrinsic properties of neurons from the pedunculopontine nucleus (PPN). Leptin reduced the amplitude of voltage-gated sodium (INa) and hyperpolarization-activated cyclic nucleotide-gated HCN (IH) channels. These effects were antagonized by a leptin receptor (OB-R) antagonist and by the G-protein antagonist GDPβ.