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HCN1 Membrane Protein Introduction

Introduction of HCN1

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) is a subunit of the HCN channels. It is encoded by the HCN1 gene. Structurally, this subunit has six transmembrane helices. Commonly, HCN channels exist in homomeric tetramer configuration and form four types of homotetramers (HCN1-HCN4). Sometimes, they can assemble in heteromeric tetramer configurations, which increases the diversity of the HCN channels. The HCN1 subunit exhibits week cAMP-sensitivity but the activation of HCN1 is the fastest of the four subtypes. HCN1 is primarily expressed in the neocortex, hippocampus, cerebellar cortex, and brainstem in the central nervous system. It has also been identified in peripheral neurons such as dorsal root and trigeminal ganglion neurons. The subcellular localization of HCN1 is Neuron-type-specific.

Basic Information of HCN1
Protein Name Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Gene Name HCN1
Aliases Brain cyclic nucleotide-gated channel 1
Organism Homo sapiens (Human)
UniProt ID O60741
Transmembrane Times 6
Length (aa) 890
Sequence MEGGGKPNSSSNSRDDGNSVFPAKASATGAGPAAAEKRLGTPPGGGGAGAKEHGNSVCFKVDGGGGGGGGGGGGEEPAGGFEDAEGPRRQYGFMQRQFTSMLQPGVNKFSLRMFGSQKAVEKEQERVKTAGFWIIHPYSDFRFYWDLIMLIMMVGNLVIIPVGITFFTEQTTTPWIIFNVASDTVFLLDLIMNFRTGTVNEDSSEIILDPKVIKMNYLKSWFVVDFISSIPVDYIFLIVEKGMDSEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDLASAVVRIFNLIGMMLLLCHWDGCLQFLVPLLQDFPPDCWVSLNEMVNDSWGKQYSYALFKAMSHMLCIGYGAQAPVSMSDLWITMLSMIVGATCYAMFVGHATALIQSLDSSRRQYQEKYKQVEQYMSFHKLPADMRQKIHDYYEHRYQGKIFDEENILNELNDPLREEIVNFNCRKLVATMPLFANADPNFVTAMLSKLRFEVFQPGDYIIREGAVGKKMYFIQHGVAGVITKSSKEMKLTDGSYFGEICLLTKGRRTASVRADTYCRLYSLSVDNFNEVLEEYPMMRRAFETVAIDRLDRIGKKNSILLQKFQKDLNTGVFNNQENEILKQIVKHDREMVQAIAPINYPQMTTLNSTSSTTTPTSRMRTQSPPVYTATSLSHSNLHSPSPSTQTPQPSAILSPCSYTTAVCSPPVQSPLAARTFHYASPTASQLSLMQQQPQQQVQQSQPPQTQPQQPSPQPQTPGSSTPKNEVHKSTQALHNTNLTREVRPLSASQPSLPHEVSTLISRPHPTVGESLASIPQPVTAVPGTGLQAGGRSTVPQRVTLFRQMSSGAIPPNRGVPPAPPPPAAALPRESSSVLNTDPDAEKPRFASNL

Functions of HCN1 Membrane Protein

The unique properties of HCNs have made them versatile regulators of neuronal excitability and activity of neuronal networks. HCN1 may play a role in mechanisms of thalamocortical oscillations, hippocampal plasticity, spatial working memory, motor learning, and nociception. An altered function of expression of HCN1 subunit in the nervous system might lead to pathological conditions. Firstly, deletion of HCN1 in mice results in greater seizure susceptibility and several studies have suggested the implication of HCN1 in the contribution of epilepsy. Secondly, HCN1 is related to the development and maintenance of neuropathic pain. HCN1 knockout mice exhibit less cold allodynia than their wild-type littermates. HCN1 channels are attractive targets to develop analgesics for the treatment of neuropathic pain.

The structure of HCN channels. Fig.1 The structure of HCN channels. (Benarroch, 2013)

Application of HCN1 Membrane Protein in Literature

  1. Zhou C., et al. HCN1 channels contribute to the effects of amnesia and hypnosis but not immobility of volatile anesthetics. Anesthesia and analgesia. 2015, 121(3): 661. PubMed ID: 26287296

    This study used global and conditional HCN1 knockout mice to evaluate how HCN1 channels affect the actions of volatile anesthetics.

  2. Schön C., et al. Loss of HCN1 enhances disease progression in mouse models of CNG channel-linked retinitis pigmentosa and achromatopsia. Human molecular genetics. 2016, 25(6): 1165-1175. PubMed ID: 26740549

    This study investigated the effects of genetic deletion of HCN1 on the function and survival of photoreceptors in a mouse model of CNGB1-linked retinitis pigmentosa (RP). The results showed that HCN1 was a major modifier of photoreceptor degeneration.

  3. Sothilingam V., et al. HCN1 channels enhance rod system responsivity in the retina under conditions of light exposure. PloS one. 2016, 11(1): e0147728. PubMed ID: 26807953

    This study investigated the role of HCN1 in rod photoreceptors for the enhancement of rode system responsivity under conditions of light exposure in Hcn1-/- Cnga3-/- animals. The results demonstrated the importance of HCN1 channels for regular vision.

  4. Kopp-Scheinpflug C., et al. Nitric oxide selectively suppresses IH currents mediated by HCN1-containing channels. The Journal of physiology. 2015, 593(7): 1685-1700. PubMed ID: 25605440

    Using the superior olivary complex, which exhibited a distinctive pattern of HCN1 and HCN2 expression, this study investigated NO modulation of the respective I(H) currents, and compared properties in wild-type and HCN1 knockout mice. The results showed that NO selectively suppressed fast HCN-mediate I(H) currents.

  5. McClure K.J., et al. Discovery of a novel series of selective HCN1 blockers. Bioorganic & medicinal chemistry letters. 2011, 21(18): 5197-5201. PubMed ID: 21824780

    This study reported the discovery of a series of novel, potent, and selective blockers of the HCN1 channel, and did a SAR study around these blockers.

HCN1 Preparation Options

Creative Biolabs is a well-recognized leading service provider of membrane protein-related services. Backed by our cutting-edge Magic™ Membrane Protein Production Platform, we can help obtain functional formats of your membrane protein of interest. Traditionally, we use detergents for membrane protein extraction, purification, and crystallization. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-HCN1 antibody development services.


However, sometimes measuring the functions and structures of membrane proteins in the detergent-solubilized state can be difficult. Therefore, we have developed various substitutive strategies to reconstitute your protein of interest into liposomes, nanodiscs, or polymers. After membrane proteins are obtained, Creative Biolabs can help the discovery of anti-membrane protein antibodies using our cutting-edge antibody development and engineering technologies. Contact us to get full advice from our experts for your membrane protein preparation or anti-membrane protein antibody discovery projects.

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