hcn3

We used a screening strategy to test for reprogramming factors for the conversion of human cardiac progenitor cells (CPCs) into Pacemaker-like cells. Human transcription factors SHOX2, TBX3, TBX5, TBX18, and the channel protein HCN2, were transiently induced as single factors and in trio combinations into CPCs, first transduced with the connexin 30.2 (CX30.2) mCherry reporter. Following screens for reporter CX30.2 mCherry gene activation and FACS enrichment, we observed the definitive expression of many pacemaker specific genes; including, CX30...

Hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN channels) are widely expressed in the central and peripheral nervous systems and organs, while their functions are not well elucidated especially in the sympathetic nerve. The present study aimed to investigate the roles of HCN channel isoforms in the differentiation of sympathetic neurons using PC12 cell as a model. PC12 cells derived from rat pheochromocytoma were cultured and induced by nerve growth factor (NGF) (25 ng/ml) to differentiate to sympathetic neuron-like cells...

Hyperpolarization-activated cationic HCN channels comprise four members (HCN1-4) that control dendritic integration, synaptic transmission and action potential firing. In the kidney, HCN1, HCN2 and HCN3 are differentially expressed and contribute to the transport of sodium, potassium (K+ ) and ammonium into the nephrons. HCN3 is regulated by K+ diets in the kidney. In this work we performed a proteomic analysis of HCN3 expressed in human embryonic kidney cells (HEK293 cells). More than 50% of the interacting proteins belonged to mitochondria...

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Alzheimer's disease (AD) is an incurable neurodegenerative disease characterized by memory loss and neurotoxic amyloid beta (Aβ) plaques accumulation. Numerous pharmacological interventions targeting Aβ plaques accumulation have failed to alleviate AD. Also, the pathological alterations in AD start years before the onset of clinical symptoms. To identify proteins at play during the early stage of AD, we conducted proteomic analysis of the hippocampus of young AppNL-F mice model of AD at the preclinical phase of the disease...

KEY POINTS: HCN ion channels conducting the Ih current control the frequency of firing in peripheral sensory neurons signalling pain. Previous studies have demonstrated a major role for the HCN2 subunit in chronic pain but the potential involvement of HCN3 in pain has not been investigated. HCN3 was found to be widely expressed in all classes of sensory neurons (small, medium, large) where it contributes to Ih . HCN3 deletion increased the firing rate of medium but not small, sensory neurons...

Mice deficient of the mitochondrial promoter peroxisome proliferator activated receptor-γ coactivator-1β ( Pgc-1β-/- ) is a valuable model for metabolic diseases and has been found to present with several pathologies including ventricular arrhythmia. In this study our aim was to shed light on the molecular mechanisms behind the observed arrhythmic substrate by studying how the expression of selected genes critical for cardiac function differs in WT compared to Pgc-1β knockout mice and young compared to aged mice...

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels generate rhythmic activity in the heart and brain. Isoform-specific functional differences reflect the specializations required for the various roles that they play. Despite a high sequence and structural similarity, HCN isoforms differ greatly in their response to cyclic nucleotides. Cyclic AMP (cAMP) enhances the activity of HCN2 and HCN4 isoforms by shifting the voltage dependence of activation to more depolarized potentials, whereas HCN1 and HCN3 isoforms are practically insensitive to this ligand...

Spontaneous rhythmic action potential or pacemaking activity of pacemaker cells controls rhythmic signaling such as heartbeat. The mechanism underlying the origin of pacemaking activity is not well understood. In this study, we created human embryonic kidney (HEK) 293 cells that show pacemaking activity through heterologous expression of strong inward rectifier K+ subfamily 2 isoform 1 (Kir2.1) channels, hyperpolarization-activated cyclic nucleotide-gated isoform 2 (HCN2) nonselective cation channels, and voltage-gated Na+ subfamily 1 isoform 5 or Ca2+ subfamily 3 isoform 1 (Nav 1...

Funny current ( I f ), formed by hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), is supposed to be crucial for the membrane clock regulating the cardiac pacemaker mechanism. We examined the presence and activity of HCN channels in the brown trout ( Salmo trutta fario ) sinoatrial (SA) pacemaker cells and their putative role in heart rate ( f H ) regulation. Six HCN transcripts (HCN1, HCN2a, HCN2ba, HCN2bb, HCN3, and HCN4) were expressed in the brown trout heart. The total HCN transcript abundance was 4...

Typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) and interstitial cells (ICs) within the pacemaker region of the mouse renal pelvis were examined using focused ion beam scanning electron (FIB SEM) tomography, immunohistochemistry and Ca2+ imaging. Individual cells within 500-900 electron micrograph stacks were volume rendered and associations with their neighbours established. 'Ribbon-shaped', Ano1 Cl- channel immuno-reactive ICs were present in the adventitia and the sub-urothelial space adjacent to the TSMC layer...

The purpose of this study was to investigate the differential expression and functional roles of long non-coding RNAs (lncRNAs) in neuroblastoma tissue. LncRNA microarrays were used to identify differentially expressed lncRNAs between tumor and para-tumor tissues. In total, in tumor tissues, 3,098 and 1,704 lncRNAs were upregulated and downregulated, respectively. HCN3 and linc01105 exhibited the higher expression (P < 0.05; P < 0.01, respectively) in neuroblastoma tissue, whereas MEG3 displayed the lower expression (P < 0...

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated pore loop channels. In mammals, this family consists of four different subunits (HCN1-4) and their ion channels activity have been proposed to play an essential role in regulating the membrane potential of excitable cells. Here, we describe the expression and relative abundances of HCN channels in cerebellum and primary cultures of cerebellar granule neurons (CGN). Quantitative determination of mRNA expression levels demonstrated the existence of an accumulation pattern of transcripts in cerebellum that encode HCN2 > HCN3 = HCN4 > HCN1 subunits...

Although hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels and the corresponding h-current (Ih) have been shown to fundamentally shape the activity pattern in the thalamocortical network, little is known about their function in local circuit GABAergic interneurons (IN) of the dorsal part of the lateral geniculate nucleus (dLGN). By combining electrophysiological, molecular biological, immunohistochemical and cluster analysis, we characterized the properties of Ih and the expression profile of HCN channels in IN...

Renal pacemaker activity triggers peristaltic upper urinary tract contractions that propel waste from the kidney to the bladder, a process prone to congenital defects that are the leading cause of pediatric kidney failure. Recently, studies have discovered that hyperpolarization-activated cation (HCN) and T-type calcium (TTC) channel conductances underlie murine renal pacemaker activity, setting the origin and frequency and coordinating upper urinary tract peristalsis. Here, we determined whether this ion channel expression is conserved in the porcine and human urinary tracts, which share a distinct multicalyceal anatomy with multiple pacemaker sites...

Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron's ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4(-) Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs...

Expression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN1-4) on distal dendrites of neurons is suggested to modify synaptic integration in the central nervous system. However, the mechanisms of dendritic localization are not fully understood. Recent studies have revealed that S-palmitoylation plays an important role in the enrichment of various molecules at the postsynaptic membrane. Thus, we performed an acyl-biotinyl exchange assay, and found that HCN1, HCN2, and HCN4, but not HCN3, were S-palmitoylated in HEK293 cells...

In rat's sensory neurons, hyperpolarization-activated inward currents (Ih) play an essential role in mediating action potentials and contributing to neuronal excitability. Classified by the size of neurons and ages, we studied the Ih and transcription levels of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels using electrophysiology and the single-cell RT-PCR. In voltage-clamp studies, Ih and half-maximal activation voltage (V1/2) changed with age and size. An analysis of all HCN subtypes in dorsal root ganglion (DRG) neurons by single-cell RT-PCR was carried out...

AIM: To determine if hyperpolarisation-activated nucleotide-gated (HCN) channels exist in human colon, and to investigate the expression of HCN channels in Hirschsprung's disease. METHODS: We investigated HCN1, HCN2, HCN3 and HCN4 protein expression in pull-through specimens from patients with Hirschsprung's disease (HSCR, n = 10) using the proximal-most ganglionic segment and distal-most aganglionic segment, as well as in healthy control specimens obtained at the time of sigmoid colostomy closure in children who had undergone anorectoplasty for imperforate anus (n = 10)...

BACKGROUND: The avalanche of integromics and panomics approaches shifted the deciphering of aging mechanisms from single molecular entities to communities of them. In this orientation, we explore the cardiac aging mechanisms - risk factor for multiple cardiovascular diseases - by capturing the micronome synergism and detecting longevity signatures in the form of communities (modules). For this, we developed a meta-analysis scheme that integrates transcriptome expression data from multiple cardiac-specific independent studies in mouse and human along with proteome and micronome interaction data in the form of multiple independent weighted networks...