Hyperpolarization-activated, Cyclic Nucleotide-gated (HCN) Channels in the Regulation of Midbrain Dopamine Systems

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2010 Aug 3

PMID 20676119

Citations 26

Authors

Hong-Yuan Chu

Xuechu Zhen

Affiliations

Soon will be listed here.

Abstract

Hyperpolarization-activated, cyclic nucleotide-gated channels (HCN channels) are expressed widely in the brain and invovled in various neuronal activities, including the control of neuronal rhythmic activity, setting the resting membrane potential, as well as dendritic integration. HCN channels also participate in the regulation of spontaneous activity of midbrain dopamine (DA) neurons to some extent. In slice preparations of midbrain, a hyperpolarization-activated non-selective cation current (Ih) mediated by the channels has been proposed as an electrophysiological marker to identify DA neurons. Recent evidence, however, shows that the functional roles of HCN channels in midbrain DA neurons are obviously underestimated. Here, we review the recent advances in the studies of the functional roles of Ih in midbrain DA neurons and further, their involvement in drug addiction and Parkinson's disease.

Citing Articles

Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

Kim D, Roh H, Lee H, Kim S, Im M Front Neuroanat. 2024; 18:1385932.

PMID: 38562955 PMC: 10982330. DOI: 10.3389/fnana.2024.1385932.

HCN channel inhibitor induces ketamine-like rapid and sustained antidepressant effects in chronic social defeat stress model.

Cai M, Zhu Y, Shanley M, Morel C, Ku S, Zhang H Neurobiol Stress. 2023; 26:100565.

PMID: 37664876 PMC: 10468802. DOI: 10.1016/j.ynstr.2023.100565.

Deficiency of Cullin 3, a Protein Encoded by a Schizophrenia and Autism Risk Gene, Impairs Behaviors by Enhancing the Excitability of Ventral Tegmental Area (VTA) DA Neurons.

Gao N, Liu Z, Wang H, Shen C, Dong Z, Cui W J Neurosci. 2023; 43(36):6249-6267.

PMID: 37558490 PMC: 10490515. DOI: 10.1523/JNEUROSCI.0247-23.2023.

Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk.

Powell S, OShea C, Townsley K, Prytkova I, Dobrindt K, Elahi R Mol Psychiatry. 2021; 28(5):1970-1982.

PMID: 34493831 PMC: 8898985. DOI: 10.1038/s41380-021-01273-0.

Generation of hiPSC-Derived Functional Dopaminergic Neurons in Alginate-Based 3D Culture.

Gilmozzi V, Gentile G, Riekschnitz D, Von Troyer M, Lavdas A, Kerschbamer E Front Cell Dev Biol. 2021; 9:708389.

PMID: 34409038 PMC: 8365765. DOI: 10.3389/fcell.2021.708389.

References

Liu Z, Bunney E, Appel S, Brodie M . Serotonin reduces the hyperpolarization-activated current (Ih) in ventral tegmental area dopamine neurons: involvement of 5-HT2 receptors and protein kinase C. J Neurophysiol. 2003; 90(5):3201-12. DOI: 10.1152/jn.00281.2003. View

Zong X, Eckert C, Yuan H, Wahl-Schott C, Abicht H, Fang L . A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase. J Biol Chem. 2005; 280(40):34224-32. DOI: 10.1074/jbc.M506544200. View

Ford C, Mark G, Williams J . Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location. J Neurosci. 2006; 26(10):2788-97. PMC: 3623681. DOI: 10.1523/JNEUROSCI.4331-05.2006. View

Zolles G, Klocker N, Wenzel D, Weisser-Thomas J, Fleischmann B, Roeper J . Pacemaking by HCN channels requires interaction with phosphoinositides. Neuron. 2006; 52(6):1027-36. DOI: 10.1016/j.neuron.2006.12.005. View

Grace A . Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience. 1991; 41(1):1-24. DOI: 10.1016/0306-4522(91)90196-u. View

Okamoto T, Harnett M, Morikawa H . Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice. J Neurophysiol. 2005; 95(2):619-26. PMC: 1454360. DOI: 10.1152/jn.00682.2005. View

Overton P, Clark D . Burst firing in midbrain dopaminergic neurons. Brain Res Brain Res Rev. 1998; 25(3):312-34. DOI: 10.1016/s0165-0173(97)00039-8. View

Mercuri N, Bonci A, Calabresi P, Stefani A, Bernardi G . Properties of the hyperpolarization-activated cation current Ih in rat midbrain dopaminergic neurons. Eur J Neurosci. 1995; 7(3):462-9. DOI: 10.1111/j.1460-9568.1995.tb00342.x. View

Mercuri N, Bonci A, Calabresi P, Stratta F, Stefani A, Bernardi G . Effects of dihydropyridine calcium antagonists on rat midbrain dopaminergic neurones. Br J Pharmacol. 1994; 113(3):831-8. PMC: 1510432. DOI: 10.1111/j.1476-5381.1994.tb17068.x. View

10.

McCormick D, Pape H . Noradrenergic and serotonergic modulation of a hyperpolarization-activated cation current in thalamic relay neurones. J Physiol. 1990; 431:319-42. PMC: 1181776. DOI: 10.1113/jphysiol.1990.sp018332. View

11.

Pape H, McCormick D . Noradrenaline and serotonin selectively modulate thalamic burst firing by enhancing a hyperpolarization-activated cation current. Nature. 1989; 340(6236):715-8. DOI: 10.1038/340715a0. View

12.

Notomi T, Shigemoto R . Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. J Comp Neurol. 2004; 471(3):241-76. DOI: 10.1002/cne.11039. View

13.

Wainger B, DeGennaro M, Santoro B, Siegelbaum S, Tibbs G . Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature. 2001; 411(6839):805-10. DOI: 10.1038/35081088. View

14.

Santoro B, Chen S, Luthi A, Pavlidis P, Shumyatsky G, Tibbs G . Molecular and functional heterogeneity of hyperpolarization-activated pacemaker channels in the mouse CNS. J Neurosci. 2000; 20(14):5264-75. PMC: 6772310. View

15.

Hornykiewicz O . Parkinson's disease: from brain homogenate to treatment. Fed Proc. 1973; 32(2):183-90. View

16.

Amini B, CLARK Jr J, Canavier C . Calcium dynamics underlying pacemaker-like and burst firing oscillations in midbrain dopaminergic neurons: a computational study. J Neurophysiol. 1999; 82(5):2249-61. DOI: 10.1152/jn.1999.82.5.2249. View

17.

Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M . A family of hyperpolarization-activated mammalian cation channels. Nature. 1998; 393(6685):587-91. DOI: 10.1038/31255. View

18.

Neuhoff H, Neu A, Liss B, Roeper J . I(h) channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain. J Neurosci. 2002; 22(4):1290-302. PMC: 6757558. View

19.

Kiyatkin E, Rebec G . Heterogeneity of ventral tegmental area neurons: single-unit recording and iontophoresis in awake, unrestrained rats. Neuroscience. 1998; 85(4):1285-309. DOI: 10.1016/s0306-4522(98)00054-2. View

20.

Rodnitzky R . Can calcium antagonists provide a neuroprotective effect in Parkinson's disease?. Drugs. 1999; 57(6):845-9. DOI: 10.2165/00003495-199957060-00001. View