Disease relevance of Cnga1

• In the present study, we investigated whether Ca(2+) can permeate through the hyperpolarization-activated pacemaker channels (HCN) expressed in HEK293 cells and I(h) channels in dorsal root ganglion (DRG) neurons [1].
• To evaluate the effect of MiRP1 on HCN expression and function in a physiological context, we used an adenovirus approach to overexpress a hemagglutinin (HA)-tagged MiRP1 (HAMiRP1) and HCN2 in neonatal rat ventricular myocytes, a cell type that expresses both MiRP1 and HCN2 message at low levels [2].
• Recent studies have implicated HCN channels in neuropathological conditions including epilepsy [3].
• The current N-Gas Model predicts the toxicity of complex fire gas mixtures based on a large data base of experimental results of individual and mixed gases that include CO, CO2, reduced O2, HCN, HCl, HBr, and NOx [4].
• Cigarette smoking during pregnancy exposes the fetus to both nicotine and hypoxia/ischemia; postnatal exposure to second-hand smoke also involves substances that cause hypoxia (CO, HCN) [5].

High impact information on Cnga1

• The I(h) channel blockers Cs(+) and ZD7288 inhibit both HCN current and Ca(2+) influx [1].
• Given the high expression levels of MiRP1 and HCN subunits in the cardiac sinoatrial node and the contribution of pacemaker channel function to impulse initiation in that tissue, such an interaction could be of considerable physiological significance [2].
• Hyperpolarization-activated channels (Ih or HCN channels) are widely expressed in principal neurons in the central nervous system [6].
• Formation of heteromeric hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the hippocampus is regulated by developmental seizures [7].
• We characterize, for the first time, single HCN currents of excised inside-out patches from somata of acutely dissociated rat hippocampal CA1 pyramidal cells [3].

Chemical compound and disease context of Cnga1

• The effectiveness of this approach was demonstrated at the National Institute of Standards and Technology (NIST) when HCN generation was reduced by 90% and the resultant toxicity of the combustion products was lowered by 50% when a flexible polyurethane foam (FPU) was treated with 0.1% (by weight) cuprous oxide (Cu2O) [8].

Biological context of Cnga1

• These changes result in long-lasting alteration of the HCN phenotype of specific hippocampal neuronal populations, with profound consequences on the excitability of the hippocampal network [9].
• The high expression of CNG1 mRNA in the endothelium of medium-sized arteries and small-sized arteries implicates a possible involvement of CNG1 protein in the regulation of blood supply to different regions and in the regulation of arterial blood pressure [10].
• 1) The large neurons had significantly higher V0.5 values (membrane potential at which the HCN channels were half-activated) and shorter time constants (tau) than small or medium-sized DRG neurons [11].
• This stimulation has been linked to the function of the cyclic nucleotide-gated cation channel, implying an important physiologic role for taurine in visual signal transduction [12].
• ZD7288 inhibits exocytosis in an HCN-independent manner and downstream of voltage-gated calcium influx in pituitary lactotrophs [13].

Anatomical context of Cnga1

• Here, we demonstrate the expression of the alpha-subunit of rod- and olfactory-type CNG channels (CNG1 and CNG2, respectively) in the rat medial vestibular nucleus (MVN) [14].
• The cellular distribution of CNG1 was further studied by in situ hybridization, which demonstrated expression of mRNA in lung, thymus, pineal gland, hippocampus, cerebellum, and cerebral cortex but not in heart or kidney [15].
• A cDNA encoding the CNG1 isoform was isolated from rat eye and human retina, and partial sequences were isolated from rat pineal gland and human kidney [15].
• Northern blot analysis revealed a 3.1-kilobase (kb) CNG1 transcript in rat eye, pineal gland, pituitary, adrenal gland, and spleen, and a larger transcript of 3.5 kb was found in testis [15].
• Polymerase chain reaction-based detection of the mRNA for CNG1 indicates that the channel is expressed in lower abundance in many other tissues, including thymus, skeletal muscle, heart, and parathyroid gland [15].

Associations of Cnga1 with chemical compounds

• Thus, although hippocampal cAMP concentrations increased over twofold during the developmental period studied, the coordinated changes in expression of three HCN channel isoforms resulted in reduced effects of this signalling molecule on neuronal h currents [16].
• Dibutyryl-cGMP, a cyclic nucleotide-gated cation channel agonist, increased alveolar fluid clearance in malnourished rats supplied with sodium glutamate [17].
• In the present study, we investigated effects of a general anesthetic, propofol, on native I(h) in neurons of thalamus and cortex and on the corresponding cloned HCN channel subunits [18].
• The third type of sensor is designed to measure low levels of toxic gases such as H2S and HCN [19].
• In addition, three investigational compounds having analgesic potential were examined: ZD-7288, a blocker of HCN channels; EAA-090, an NMDA antagonist; and WAY-132983, a muscarinic agonist [20].

Other interactions of Cnga1

• Nested polymerase chain reaction revealed CNG channel mRNA in the MVN, and CNG1 and CNG2 proteins were also detected by Western blotting and immunohistochemistry [14].

Analytical, diagnostic and therapeutic context of Cnga1

• We used Northern blot analysis, ribonuclease protection assay (RPA), reverse transcriptase-polymerase chain reaction, and in situ hybridization to investigate the hypothesis that the CNG1 isoform of the cyclic nucleotide-gated nonselective cation channel may be widely distributed in tissues of the rat [15].
• METHODS: We used RT-PCR, molecular cloning, northern Blot and in situ hybridization to examine the expression of CNG1 mRNA in a variety of guinea pig and rat blood vessels with different diameters and in cultured vascular endothelial cells and vascular smooth muscle cells [10].
• RT-PCR and southern blot results indicate that the CNG1 mRNA is expressed in both cultured vascular endothelial and cultured vascular SMCs [10].
• Finally, nested-polymerase chain reaction assay revealed the expression of CNG channel alpha subunit transcript in MVNn [21].
• We therefore used whole cell patch-clamp techniques to investigate the properties of hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents (I(h)) in dorsal root ganglion (DRG) neurons innervating the urinary bladder of rats [22].

References