scholarly journals Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?

Channels ◽  
2012 ◽  
Vol 6 (6) ◽  
pp. 438-442 ◽  
Author(s):  
Xing Wu ◽  
Liping Liao ◽  
Xiangming Liu ◽  
Fang Luo ◽  
Tianming Yang ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Gated Channel ◽  
Channel Currents ◽  
Selective Blocker

Decreased Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Activity in a Rat Model of Absence Epilepsy and the Effect of ZD7288, an Ih Inhibitor, on the Spike-and-Wave Discharges

Pharmacology ◽  
2022 ◽  
pp. 1-8
Author(s):  
Melis Yavuz ◽  
Banu Aydın ◽  
Nihan Çarçak ◽  
Filiz Onat
Keyword(s):  
Rat Model ◽  
Cyclic Nucleotide ◽  
Total Duration ◽  
Absence Epilepsy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Hcn Channels ◽  
Hcn Channel ◽  
Gated Channel ◽  
Channel Currents

<b><i>Introduction:</i></b> Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents of <i>Ih</i> and absence epilepsy seizures are associated, but studies reveal differential results. <b><i>Objective:</i></b> In our study, we aimed to investigate the role of the HCN channels on the expression of spike-and-wave discharges (SWDs) using the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model. <b><i>Methods:</i></b> HCN isoform levels from isolated brains of both naïve nonepileptic Wistar and GAERS groups were evaluated by enzyme-linked immunosorbent assay. ZD7288, an <i>Ih</i> inhibitor as well as an HCN channel antagonist, was administered intracerebroventricularly to the adult GAERS groups, and to evaluate their SWD activities, electroencephalography was recorded. The effect of ZD7288 on the cumulative total duration and number of SWDs and the mean duration of each SWD complex was evaluated. <b><i>Results:</i></b> The HCN2 levels in the cortex and hippocampus of the GAERS group were lower compared to the naïve nonepileptic Wistar group (<i>p</i> &#x3c; 0.05). ZD7288 increased the number of SWDs at the 20th and 120th min with the highest administered dose of 7 μg (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> The <i>Ih</i> inhibitor ZD7288 increased the number of SWDs in a genetic absence epilepsy rat model, although this increase may not be significant due to the inconsistent time-dependent effects. In GAERS, the cortical and hippocampal HCN2 channel levels were significantly lower compared to the control group. Further studies are needed with higher doses of ZD7288 to determine if the effects will increase drastically.

Electrophysiological Characteristics of Rat Gustatory Cyclic Nucleotide–Gated Channel Expressed in Xenopus Oocytes

2001 ◽  
Vol 85 (6) ◽  
pp. 2335-2349 ◽  
Author(s):  
Han Mi Lee ◽  
Young Sun Park ◽  
Wonjae Kim ◽  
Chul-Seung Park
Keyword(s):  
Cyclic Nucleotide ◽  
Xenopus Oocytes ◽  
Single Channel ◽  
Divalent Cations ◽  
Epithelial Tissue ◽  
Dna Encoding ◽  
Open Probability ◽  
Voltage Dependent ◽  
Gated Channel ◽  
Channel Currents

The complementary DNA encoding gustatory cyclic nucleotide–gated ion channel (or gustCNG channel) cloned from rat tongue epithelial tissue was expressed in Xenopus oocytes, and its electrophysiological characteristics were investigated using tight-seal patch-clamp recordings of single and macroscopic channel currents. Both cGMP and cAMP directly activated gustCNG channels but with markedly different affinities. No desensitization or inactivation of gustCNG channel currents was observed even in the prolonged application of the cyclic nucleotides. Single-channel conductance of gustCNG channel was estimated as 28 pS in 130 mM of symmetric Na+. Single-channel current recordings revealed fast open-close transitions and longer lasting closure states. The distribution of both open and closed events could be well fitted with two exponential components and intracellular cGMP increased the open probability ( P o) of gustCNG channels mainly by increasing the slower opening rate. Under bi-ionic conditions, the selectivity order of gustCNG channel among divalent cations was determined as Na+ ∼ K+ > Rb+ > Li+ > Cs+ with the permeability ratio of 1:0.95:0.74:0.63:0.49. Magnesium ion blocked Na+ currents through gustCNG channels from both intracellular and extracellular sides in voltage-dependent manners. The inhibition constants ( K is) of intracellular Mg2+ were determined as 360 ± 40 μM at 70 mV and 8.2 ± 1.5 mM at −70 mV with zδ value of 1.04, while K is of extracellular Mg2+ were as 1.1 ± 0.3 mM at 70 mV and 20.0 ± 0.1 μM at −70 mV with zδ of 0.94. Although 100 μM l- cis-diltiazem blocked significant portions of outward Na+ currents through both bovine rod and rat olfactory CNG channels, the gustCNG channel currents were minimally affected by the same concentration of the drug.

scholarly journals Systemic administration of ivabradine, a hyperpolarization‐activated cyclic nucleotide‐gated channel inhibitor, blocks spontaneous absence seizures

Epilepsia ◽  
2021 ◽  
Author(s):  
Yasmine Iacone ◽  
Tatiana P. Morais ◽  
François David ◽  
Francis Delicata ◽  
Joanna Sandle ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Systemic Administration ◽  
Absence Seizures ◽  
Gated Channel

Expression of the olfactory cyclic nucleotide gated channel (CNG1) in the rat brain

Neuroreport ◽  
1995 ◽  
Vol 6 (10) ◽  
pp. 1459-1463 ◽  
Author(s):  
Alaa El-Din El-Husseini ◽  
Christopher Bladen ◽  
Steven R. Vincent
Keyword(s):  
Rat Brain ◽  
Cyclic Nucleotide ◽  
Gated Channel

Impaired Opsin Targeting and Cone Photoreceptor Migration in the Retina of Mice Lacking the Cyclic Nucleotide-Gated Channel CNGA3

2005 ◽  
Vol 46 (4) ◽  
pp. 1516 ◽  
Author(s):  
Stylianos Michalakis ◽  
Heidi Geiger ◽  
Silke Haverkamp ◽  
Franz Hofmann ◽  
Andrea Gerstner ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Cone Photoreceptor ◽  
Gated Channel
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