Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
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 a...
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todo:paper_00223042_v126_n6_p705_Beck2023-10-03T14:30:50Z Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons Beck, P. Mahaffey, S. Urbano, F.J. Garcia-Rill, E. arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current guanine nucleotide binding protein leptin leptin receptor n methyl dextro aspartic acid receptor proton pump sodium channel animal cell animal tissue article brain nerve cell brain slice brain stem controlled study female male nonhuman patch clamp pedunculopontine tegmental nucleus priority journal protein function rat arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current Animals Cyclic Nucleotide-Gated Cation Channels Data Interpretation, Statistical Excitatory Postsynaptic Potentials Female GTP-Binding Proteins Immunohistochemistry Leptin Male Membrane Potentials Neurons Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Population Potassium Channels Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate Sodium Channels Rattus 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. 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. © 2013 International Society for Neurochemistry. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00223042_v126_n6_p705_Beck |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current guanine nucleotide binding protein leptin leptin receptor n methyl dextro aspartic acid receptor proton pump sodium channel animal cell animal tissue article brain nerve cell brain slice brain stem controlled study female male nonhuman patch clamp pedunculopontine tegmental nucleus priority journal protein function rat arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current Animals Cyclic Nucleotide-Gated Cation Channels Data Interpretation, Statistical Excitatory Postsynaptic Potentials Female GTP-Binding Proteins Immunohistochemistry Leptin Male Membrane Potentials Neurons Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Population Potassium Channels Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate Sodium Channels Rattus |
| spellingShingle |
arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current guanine nucleotide binding protein leptin leptin receptor n methyl dextro aspartic acid receptor proton pump sodium channel animal cell animal tissue article brain nerve cell brain slice brain stem controlled study female male nonhuman patch clamp pedunculopontine tegmental nucleus priority journal protein function rat arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current Animals Cyclic Nucleotide-Gated Cation Channels Data Interpretation, Statistical Excitatory Postsynaptic Potentials Female GTP-Binding Proteins Immunohistochemistry Leptin Male Membrane Potentials Neurons Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Population Potassium Channels Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate Sodium Channels Rattus Beck, P. Mahaffey, S. Urbano, F.J. Garcia-Rill, E. Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons |
| topic_facet |
arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current guanine nucleotide binding protein leptin leptin receptor n methyl dextro aspartic acid receptor proton pump sodium channel animal cell animal tissue article brain nerve cell brain slice brain stem controlled study female male nonhuman patch clamp pedunculopontine tegmental nucleus priority journal protein function rat arousal GDPβ, GTPγS hyperpolarization-activated cation current sodium current Animals Cyclic Nucleotide-Gated Cation Channels Data Interpretation, Statistical Excitatory Postsynaptic Potentials Female GTP-Binding Proteins Immunohistochemistry Leptin Male Membrane Potentials Neurons Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Population Potassium Channels Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate Sodium Channels Rattus |
| description |
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. 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. © 2013 International Society for Neurochemistry. |
| format |
JOUR |
| author |
Beck, P. Mahaffey, S. Urbano, F.J. Garcia-Rill, E. |
| author_facet |
Beck, P. Mahaffey, S. Urbano, F.J. Garcia-Rill, E. |
| author_sort |
Beck, P. |
| title |
Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons |
| title_short |
Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons |
| title_full |
Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons |
| title_fullStr |
Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons |
| title_full_unstemmed |
Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons |
| title_sort |
role of g-proteins in the effects of leptin on pedunculopontine nucleus neurons |
| url |
http://hdl.handle.net/20.500.12110/paper_00223042_v126_n6_p705_Beck |
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