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Role of G-proteins in the Effects of Leptin on Pedunculopontine Nucleus Neurons

Role of G-proteins in the Effects of Leptin on Pedunculopontine Nucleus Neurons

Paige Beck, Susan Mahaffey, Francisco J Urbano, Edgar Garcia-Rill

J Neurochem. 2013 Sep;126(6):705-14.

PMID: 23692342

Abstract:

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 (I(Na)) and h-current (I(H)) in PPN neurons. TA (100 nM) reduced the blockade of I(Na) (~ 50% reduction) and I(H) (~ 93% reduction) caused by leptin. Intracellular guanosine 5'-[β-thio]diphosphate trilithium salt (a G-protein inhibitor) significantly reduced the effect of leptin on I(Na) (~ 60% reduction) but not on I(H) (~ 25% reduction). Intracellular GTPγS (a G-protein activator) reduced the effect of leptin on both I(Na) (~ 80% reduction) and I(H) (~ 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 (I(Na)) and hyperpolarization-activated cyclic nucleotide-gated HCN (I(H)) channels. These effects were antagonized by a leptin receptor (OB-R) antagonist and by the G-protein antagonist GDPβ.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP97952368	Guanosine 5′-[β-thio]diphosphate trilithium salt		97952-36-8	Price

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