Hyperpolarization-activated, Cyclic Nucleotide-gated Channel Assays
Background of Hyperpolarization-activated, Cyclic Nucleotide-gated Channel
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, also known as pacemaker channels, are integral membrane proteins belonging to the voltage-gated pore loop channels family. They have served as nonselective voltage-gated cation channels in the plasma membranes of both heart and brain cells.
Expression and Functions of Hyperpolarization-activated, Cyclic Nucleotide-gated Channel
Encoded by four genes, HCN1, 2, 3, and 4, HCN channels are widely expressed throughout the heart and the central nervous system. These four different isoforms can assemble to form homo- or hetero-tetramers with different biophysical properties. Activation of HCN channels via membrane hyperpolarization allows the permeability of Na+ and K+ and is involved in different physiologic processes. This activation process can be blocked by millimolar concentrations of extracellular Cs+ and is regulated by cyclic nucleotides, especially cAMP.
Fig.1. HCN channel topology and associated interacting proteins. (Sartiani, 2017)
Diseases Associated with Hyperpolarization-activated, Cyclic Nucleotide-gated Channel
Studies have shown that genetic defects and altered expression of HCN channels are associated with several pathologies. Currently, a drug has been developed to specifically block hyperpolarization-activated currents. As key regulators of neuronal excitability and network activity within the nervous system, HCN channels have been identified as potential therapeutic targets for several neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS).
Assay List of Hyperpolarization-activated, Cyclic Nucleotide-gated Channels
Creative Biolabs can provide a range of assays of hyperpolarization-activated, cyclic nucleotide-gated channels. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Hyperpolarization-activated cyclic nucleotide-gated channels as drug targets for neurological disorders |
| Journal | Annual Review of Pharmacology and Toxicology |
| Published | 2020 |
| Abstract | Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels act as voltage-gated ion channels to tightly regulate neuronal activity. Each of the four HCN subunits (HCN1–4) has distinct expression profiles and unique effects on neuronal excitability in the brain. In this paper, we describe the structure and distribution of individual HCN channel subtypes, their effects on neuronal activity under physiological conditions, and their expression and function in neurological diseases. Ultimately, we believe that HCN channels or their accessory subunit TRIP8b can serve as potential targets for the treatment of different neurological diseases. |
| Result |
In recent years, there has been substantial evidence that HCN channels may serve as valuable targets for the treatment of many neurological diseases. Therefore, strategies to develop compounds with selective HCN isoform specificity are urgently needed. These newly developed compounds have been endowed with the ability to cross the blood-brain barrier to treat central dysfunction. Finally, the development of compounds that specifically activate rather than block HCN channels may offer additional extraordinary opportunities for the treatment of different neurological and neuropsychiatric disorders.
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Fig.2. Structure of the HCN1 channel. (Santoro & Shah, 2020)
References
- Sartiani, L.; et al. The hyperpolarization-activated cyclic nucleotide–gated channels: from biophysics to pharmacology of a unique family of ion channels. Pharmacological reviews. 2017, 69(4): 354-395.
- Santoro, B.; Shah, M.M. Hyperpolarization-activated cyclic nucleotide-gated channels as drug targets for neurological disorders. Annual Review of Pharmacology and Toxicology. 2020, 60: 109-131.
