Potassium Channel Block by a Tripartite Complex of Neutral Ligands with a Potassium Ion

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.

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The study of sodium and potassium channel gene single-nucleotide variation significance in non-mechanical forms of epilepsy

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-020-00123-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ozada Khamdiyeva ◽

Zhanerke Tileules ◽

Gulminyam Baratzhanova ◽

Anastassiya Perfilyeva ◽

Leyla Djansugurova

Keyword(s):

Ion Channel ◽

Potassium Channel ◽

De Novo ◽

Potassium Ion ◽

Dravet Syndrome ◽

De Novo Mutations ◽

Single Nucleotide ◽

Channel Gene ◽

Sodium And Potassium ◽

Potassium Channel Gene

Abstract Background Epilepsy is one of the most common and heterogeneous neurological diseases. The main clinical signs of the disease are repeated symptomatic or idiopathic epileptic seizures of both convulsive and non-convulsive nature that develop against a background of lost or preserved consciousness. The genetic component plays a large role in the etiology of idiopathic forms of epilepsy. The study of the molecular genetic basis of neurological disorders has led to a rapidly growing number of gene mutations known to be involved in hereditary ion channel dysfunction. The aim of this research was to evaluate the involvement of single-nucleotide variants that modify the function of genes (SCN1A, KCNT1, KCNTС1, and KCNQ2) encoding sodium and potassium ion channel polypeptides in the development of epilepsy. Results De novo mutations in the sodium channel gene SCN1A c.5347G>A (p. Ala1783Thr) were detected in two patients with Dravet syndrome, with a deletion in exon 26 found in one. Three de novo mutations in the potassium channel gene KCNT1 c.2800G>A (p. Ala934Thr), were observed in two patients with temporal lobe epilepsy (TLE) and one patient with residual encephalopathy. Moreover, a control cohort matched to the case cohort did not reveal any SNVs among conditionally healthy individuals, supporting the pathogenic significance of the studied SNVs. Conclusion Our results are supported by literature data showing that the sodium ion channel gene SCN1A c.5347G>A mutation may be involved in the pathogenesis of Dravet syndrome. We also note that the c.2800G>A mutation in the potassium channel gene KCNT1 can cause not only autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) but also other forms of epilepsy. To treat pathogenetic mutations that accelerate the function of sodium and potassium ion channels, we recommend ion channel blockade drug therapy.

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Synthetic Peptide Fragments as Probes for Structure Determination of Potassium Ion-Channel Proteins

Bioscience Reports ◽

10.1023/a:1020257215577 ◽

1998 ◽

Vol 18 (6) ◽

pp. 299-312 ◽

Cited By ~ 6

Author(s):

Parvez I. Haris

Keyword(s):

Potassium Channels ◽

Ion Channel ◽

Potassium Channel ◽

Synthetic Peptide ◽

Potassium Ion ◽

Channel Structure ◽

Phospholipid Membranes ◽

Peptide Fragments ◽

2D Nmr Spectroscopy ◽

Channel Proteins

Potassium channels are a diverse class of transmembrane proteins that are responsible for diffusion of potassium ion across cell membranes. The lack of large quantities of these proteins from natural sources, is a major hindrance in their structural characterization using biophysical techniques. Synthetic peptide fragments corresponding to functionally important domains of these proteins provide an attractive approach towards characterizing the structural organization of these ion-channels. Conformational properties of peptides from three different potassium channels (Shaker, ROMK1 and minK) have been characterized in aqueous media, organic solvents and in phospholipid membranes. Techniques used for these studies include FTIR, CD and 2D-NMR spectroscopy. FTIR spectroscopy has been a particularly valuable tool for characterizing the folding of the ion-channel peptides in phospholipid membranes; the three different types of potassium channels all share a common transmembrane folding pattern that is composed of a predominantly α-helical structure. There is no evidence to suggest the presence of any significant β-sheet structure. These results are in excellent agreement with the crystal structure of a bacterial potassium channel (Doyle, D. A. et al. (1998) Science280:69–77), and suggest that all potassium channel proteins may share a common folding motif where the ion-channel structure is constructed entirely from α-helices.

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