ArticleBritish journal of pharmacology2013
MPP(+) -dependent inhibition of Ih reduces spontaneous activity and enhances EPSP summation in nigral dopamine neurons.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Effect of Bushen Huoxue Granule on Clearance of Pathological α-Synuclein in MPPChinese journal of integrative medicine · 2025Article
- Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.Frontiers in neuroanatomy · 2024Review
- Pathophysiological Features of Nigral Dopaminergic Neurons in Animal Models of Parkinson's Disease.International journal of molecular sciences · 2022Review
- Electrophysiological Quality Control of Human Dopaminergic Neurons: Are We Doing Enough?Frontiers in cellular neuroscience · 2021Article
- Cardiac and neuronal HCN channelopathies.Pflugers Archiv : European journal of physiology · 2020Review
- Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: An Emerging Role in Neurodegenerative Diseases.Frontiers in molecular neuroscience · 2019Review
- Endogenous HCN Channels Modulate the Firing Activity of Globus Pallidus Neurons in Parkinsonian Animals.Frontiers in aging neuroscience · 2019Article
- Dynamical Mechanism of Hyperpolarization-Activated Non-specific Cation Current Induced Resonance and Spike-Timing Precision in a Neuronal Model.Frontiers in cellular neuroscience · 2018Article
- The Hyperpolarization-Activated Current Determines Synaptic Excitability, Calcium Activity and Specific Viability of Substantia Nigra Dopaminergic Neurons.Frontiers in cellular neuroscience · 2017Article
- HCN Channels Modulators: The Need for Selectivity.Current topics in medicinal chemistry · 2016Review
- High dendritic expression of Ih in the proximity of the axon origin controls the integrative properties of nigral dopamine neurons.The Journal of physiology · 2015Article
- Dysfunctional HCN ion channels in neurological diseases.Frontiers in cellular neuroscience · 2015Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purpose1-Methyl-4-phenylpyridinium (MPP(+) ), a potent parkinsonizing agent in primates and rodents, is a blocker of mitochondrial complex I, therefore MPP(+) -induced parkinsonism is believed to depend largely on mitochondrial impairment. However, it has recently been proposed that other mechanisms may participate in MPP(+) -induced toxicity. We tackled this issue by probing the effects of an acute application of MPP(+) on substantia nigra pars compacta (SNc) dopamine (DA) neurons. EXPERIMENTAL APPROACH: The effects of MPP(+) on SNc DA neurons in acute midbrain slices were investigated with electrophysiology techniques. KEY
resultsMPP(+) (50 μM) was able to (i) hyperpolarize SNc DA neurons by ∼6 mV; (ii) cause an abrupt and marked (over 50%) reduction of the spontaneous activity; and (iii) inhibit the hyperpolarization-activated inward current (Ih ). MPP(+) shifted Ih activation curve towards negative potentials by ∼11 mV both in Wistar rats and in C57/BL6 mice. Inhibition was voltage- and concentration-dependent (Imax = 47%, IC50 = 7.74 μM). MPP(+) slowed Ih activation kinetics at all potentials. These effects were not dependent on (i) block of mitochondrial complex I/fall of ATP levels; (ii) activation of type 2 DA receptor; and (iii) alteration of cAMP metabolism. Finally, MPP(+) -dependent inhibition of Ih facilitated temporal summation of evoked EPSPs in SNc DA, but not in CA1 hippocampal neurons. CONCLUSION AND IMPLICATIONS: Reduced functionality of Ih in SNc DA neurons, via increased responsiveness towards synaptic excitation, might play a role in MPP(+) -induced parkinsonism and, possibly, in the pathogenesis of human Parkinson's.
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