Inverse Modulation of Neuronal Kv12.1 and Kv11.1 Channels by 4-Aminopyridine and NS1643

@article{Dierich2018InverseMO,
 title={Inverse Modulation of Neuronal Kv12.1 and Kv11.1 Channels by 4-Aminopyridine and NS1643},
 author={Marlen Dierich and Saskia Evers and Bettina U. Wilke and Michael G. Leitner},
 journal={Frontiers in Molecular Neuroscience},
 year={2018},
 volume={11},
 url={https://api.semanticscholar.org/CorpusID:3343518}
}
Identification of currents in native cell types with mode shift that are activated through 4-AP and inhibited by NS1643 can provide strong evidence for contribution of Kv12.1-mediated currents.

9 Citations

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63 References

Modulation of Closed−State Inactivation in Kv2.1/Kv6.4 Heterotetramers as Mechanism for 4−AP Induced Potentiation
It is demonstrated that KvS subunits modify the pharmacological response of Kv2 subunits when assembled in heterotetramers and illustrate the potential of K vS sub units to provide unique pharmacological properties to the heterotETramers, as is the case for 4−AP on Kv 2.1/Kv6.4 channels.

Differential Expression of Genes Encoding Subthreshold-Operating Voltage-Gated K+ Channels in Brain
The results show that each EAG subunit has a specific pattern of expression in rat brain, and indicates that the subthreshold current in many neurons may be complex, containing different components mediated by a number of channels with distinct properties and neuromodulatory responses.

Molecular mechanism of voltage-dependent potentiation of KCNH potassium channels
It is proposed that the activation of ELK channels involves a slow open-state dependent rearrangement of the direct interaction between the eag domain and CNBHD, which stabilizes the opening of the channel.

External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor
The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels.

Functional Analysis of a Mouse Brain Elk-Type K+Channel
A mouse gene is identified, Melk2, that encodes a predicted polypeptide with 48% amino acid identity to Drosophila Elk but only 40 and 36% identity with mouse Erg (Merg) and Eag (Meag), respectively, which should aid in identification of native counterparts to the Elk subfamily of channels in the nervous system.

Ether‐à‐go‐go‐related gene K+ channels contribute to threshold excitability of mouse auditory brainstem neurons
It is concluded that ERG currents complement Kv1 currents in limiting AP firing at around threshold; ERG may have a particular role during periods of high activity when [K+]o is elevated, and suggest a potential link between auditory hyperexcitability and acoustic startle triggering of cardiac events in familial LQT2.

Kv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders
An overview of the expression of KvS subunits in different tissues is provided and their proposed role in various physiological and pathophysiological processes are discussed and the importance of considering Kv2/KvS heterotetramers in the development of novel treatments is demonstrated.

Extracellular potassium effects are conserved within the rat erg K+ channel family
The data demonstrate that most [K+]o‐dependent changes in the biophysical properties are well conserved within the erg K+ channel family, despite gradual differences in the magnitude of the effects.

4‐Aminopyridine: a pan voltage‐gated potassium channel inhibitor that enhances Kv7.4 currents and inhibits noradrenaline‐mediated contraction of rat mesenteric small arteries
The aim of this study was to investigate the pharmacological activity of 4‐AP on Kv 7.4 and Kv7.5 channels and characterize the effect of 4•AP on rat resistance arteries.

Disruption of the Ether-à-go-go K+ Channel Gene BEC1/KCNH3 Enhances Cognitive Function
BEC1 knock-out mice performed behavioral tasks related to working memory, reference memory, and attention better than their wild-type littermates and could represent the first K+ channel that contributes preferentially and bidirectionally to cognitive function.
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