Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 is a protein that in humans is encoded by the HCN1 gene. [5] [6] [7] [8]
Hyperpolarization-activated cation channels of the HCN gene family, such as HCN1, contribute to spontaneous rhythmic activity in both heart and brain. [8]
HCN1 channel expression is found in the sinoatrial node, [9] [10] the neocortex, hippocampus, cerebellar cortex, dorsal root ganglion, trigeminal ganglion and brainstem. [11] [12] [13] [14] [15]
Cyclic adenosine monophosphate is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway.
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.
Cyclic nucleotide–gated ion channels or CNG channels are ion channels that function in response to the binding of cyclic nucleotides. CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. Their function can be the result of a combination of the binding of cyclic nucleotides and either a depolarization or a hyperpolarization event. Initially discovered in the cells that make up the retina of the eye, CNG channels have been found in many different cell types across both the animal and the plant kingdoms. CNG channels have a very complex structure with various subunits and domains that play a critical role in their function. CNG channels are significant in the function of various sensory pathways including vision and olfaction, as well as in other key cellular functions such as hormone release and chemotaxis. CNG channels have also been found to exist in prokaryotes, including many spirochaeta, though their precise role in bacterial physiology remains unknown.
The pacemaker current is an electric current in the heart that flows through the HCN channel or pacemaker channel. Such channels are important parts of the electrical conduction system of the heart and form a component of the natural pacemaker.
Rap guanine nucleotide exchange factor 3 also known as exchange factor directly activated by cAMP 1 (EPAC1) or cAMP-regulated guanine nucleotide exchange factor I (cAMP-GEFI) is a protein that in humans is encoded by the RAPGEF3 gene.
Calcium-activated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNMB1 gene.
G protein-activated inward rectifier potassium channel 4(GIRK-4) is a protein that in humans is encoded by the KCNJ5 gene and is a type of G protein-gated ion channel.
Chloride channel protein 2 is a protein that in humans is encoded by the CLCN2 gene. Mutations of this gene have been found to cause leukoencephalopathy and Idiopathic generalised epilepsy, although the latter claim has been disputed. CLCN2 contains a transmembrane region that is involved in chloride ion transport as well two intracellular copies of the CBS domain.
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 is a protein that in humans is encoded by the HCN2 gene.
Cyclic nucleotide-gated cation channel alpha-3 is a protein that in humans is encoded by the CNGA3 gene.
Potassium voltage-gated channel, Isk-related family, member 3 (KCNE3), also known as MinK-related peptide 2(MiRP2) is a protein that in humans is encoded by the KCNE3 gene.
Cyclic nucleotide-gated channel alpha 1, also known as CNGA1, is a human gene encoding an ion channel protein. Heterologously expressed CNGA1 can form a functional channel that is permeable to calcium. In rod photoreceptors, however, CNGA1 forms a heterotetramer with CNGB1 in a 3:1 ratio. The addition of the CNGB1 channel imparts altered properties including more rapid channel kinetics and greater cAMP-activated current. When light hits rod photoreceptors, cGMP concentrations decrease causing rapid closure of CNGA1/B1 channels and, therefore, hyperpolarization of the membrane potential.
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene.
Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels are integral membrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of heart and brain cells. HCN channels are sometimes referred to as pacemaker channels because they help to generate rhythmic activity within groups of heart and brain cells. HCN channels are activated by membrane hyperpolarization, are permeable to Na + and K +, and are constitutively open at voltages near the resting membrane potential. HCN channels are encoded by four genes and are widely expressed throughout the heart and the central nervous system.
Sodium channel protein type 8 subunit alpha also known as Nav1.6 is a membrane protein encoded by the SCN8A gene. Nav1.6 is one sodium channel isoform and is the primary voltage-gated sodium channel at each node of Ranvier. The channels are highly concentrated in sensory and motor axons in the peripheral nervous system and cluster at the nodes in the central nervous system.
Cyclic nucleotide gated channel alpha 2, also known as CNGA2, is a human gene encoding an ion channel protein.
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 is a protein that in humans is encoded by the HCN3 gene.
The medial septal nucleus (MS) is one of the septal nuclei. Neurons in this nucleus give rise to the bulk of efferents from the septal nuclei. A major projection from the medial septal nucleus terminates in the hippocampal formation.
Lisa Monteggia is an American neuroscientist who is a Professor in the Department of Pharmacology, Psychiatry & Psychology as well as the Barlow Family Director of the Vanderbilt Brain Institute at Vanderbilt University in Nashville, Tennessee. Monteggia probes the molecular mechanisms underlying psychiatric disorders and has made critical discoveries about the role of the neurotrophins in antidepressant efficacy, the antidepressant mechanisms of Ketamine, as well as the epigenetic regulation of synaptic transmission by MeCP2.
Dario DiFrancesco is a Professor Emeritus (Physiology) at the University of Milano. In 1979, he and collaborators discovered the so-called "funny" current in cardiac pacemaker cells, a new mechanism involved in the generation of cardiac spontaneous activity and autonomic regulation of heart rate. That initiated a new field of research in the heart and brain, where hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular components of "funny" channels cloned in the late 90's, are today known to play fundamental roles in health and disease. Clinically relevant exploitation of the properties of "funny" channels has developed a channel blocker with specific heart rate-slowing action, ivabradine, marketed for the therapy of coronary artery disease, heart failure and the symptomatic treatment of chronic stable angina.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.