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Pharmacology of Potassium Channels

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 7062

Special Issue Editors


E-Mail Website
Guest Editor
Department of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037 Marburg, Germany
Interests: ion channels; potassium channels; ion channel; pharmacology; molecular composition

E-Mail Website
Guest Editor
Department of Physiology and Pathophysiology, Philipps-Universität Marburg, Marburg, Germany
Interests: ion channels; potassium channels; ion channel; pharmacology; molecular composition

Special Issue Information

Dear Colleagues, 

Ion channel pharmacology is an important aspect of drug research, as many drugs acts by modulating these membrane-bound channels. Among these ion channels, potassium channels set the resting membrane potential of almost all animal cells and are, because of their diversity and high number of members, regarded as one of the most complex families of ion channels. Many potassium channels are already regarded as new promising targets for various diseases. Although many discoveries have been accomplished in the last decades, there are still many questions about their role in the human physiology, their molecular structure and function, and especially their precise pharmacological modulation.

This Special Issue aims to illustrate established and novel knowledge on all aspects of the pharmacology of potassium channels. We invite researchers of all fields—physicians, pharmacologists, biologists, chemists, etc.—to present their results and propose prospective applications by contributing original research articles or review papers. Manuscripts may deal with the findings obtained in patients or animal models in vivo, as well as on tissues and cells in vitro.

Prof. Dr. Niels Decher
Dr. Aytug Kiper
Guest Editors

Manuscript Submission Information

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Keywords

  • potassium
  • potassium channels
  • ion channel
  • pharmacology

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Published Papers (2 papers)

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Research

19 pages, 1753 KiB  
Article
New Insights into Ion Channels: Predicting hERG-Drug Interactions
by Michael Fitzpatrick Wempe
Int. J. Mol. Sci. 2022, 23(18), 10732; https://doi.org/10.3390/ijms231810732 - 14 Sep 2022
Cited by 2 | Viewed by 2927
Abstract
Drug-induced long QT syndrome can be a very dangerous side effect of existing and developmental drugs. In this work, a model proposed two decades ago addressing the ion specificity of potassium channels is extended to the human ether-à-gogo gene (hERG). hERG encodes the [...] Read more.
Drug-induced long QT syndrome can be a very dangerous side effect of existing and developmental drugs. In this work, a model proposed two decades ago addressing the ion specificity of potassium channels is extended to the human ether-à-gogo gene (hERG). hERG encodes the protein that assembles into the potassium channel responsible for the delayed rectifier current in ventricular cardiac myocytes that is often targeted by drugs associated with QT prolongation. The predictive value of this model can guide a rational drug design decision early in the drug development process and enhance NCE (New Chemical Entity) retention. Small molecule drugs containing a nitrogen that can be protonated to afford a formal +1 charge can interact with hERG to prevent the repolarization of outward rectifier currents. Low-level ab initio calculations are employed to generate electronic features of the drug molecules that are known to interact with hERG. These calculations were employed to generate structure–activity relationships (SAR) that predict whether a small molecule drug containing a protonated nitrogen has the potential to interact with and inhibit the activity of the hERG potassium channels of the heart. The model of the mechanism underlying the ion specificity of potassium channels offers predictive value toward optimizing drug design and, therefore, minimizes the effort and expense invested in compounds with the potential for life-threatening inhibitory activity of the hERG potassium channel. Full article
(This article belongs to the Special Issue Pharmacology of Potassium Channels)
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17 pages, 3850 KiB  
Article
KCa1.1 K+ Channel Inhibition Overcomes Resistance to Antiandrogens and Doxorubicin in a Human Prostate Cancer LNCaP Spheroid Model
by Susumu Ohya, Junko Kajikuri, Kyoko Endo, Hiroaki Kito and Miki Matsui
Int. J. Mol. Sci. 2021, 22(24), 13553; https://doi.org/10.3390/ijms222413553 - 17 Dec 2021
Cited by 13 | Viewed by 3211
Abstract
Several types of K+ channels play crucial roles in tumorigenicity, stemness, invasiveness, and drug resistance in cancer. Spheroid formation of human prostate cancer (PC) LNCaP cells with ultra-low attachment surface cultureware induced the up-regulation of cancer stem cell markers, such as NANOG, [...] Read more.
Several types of K+ channels play crucial roles in tumorigenicity, stemness, invasiveness, and drug resistance in cancer. Spheroid formation of human prostate cancer (PC) LNCaP cells with ultra-low attachment surface cultureware induced the up-regulation of cancer stem cell markers, such as NANOG, and decreased the protein degradation of the Ca2+-activated K+ channel KCa1.1 by down-regulating the E3 ubiquitin ligase, FBXW7, compared with LNCaP monolayers. Accordingly, KCa1.1 activator-induced hyperpolarizing responses were larger in isolated cells from LNCaP spheroids. The pharmacological inhibition of KCa1.1 overcame the resistance of LNCaP spheroids to antiandrogens and doxorubicin (DOX). The protein expression of androgen receptors (AR) was significantly decreased by LNCaP spheroid formation and reversed by KCa1.1 inhibition. The pharmacological and genetic inhibition of MDM2, which may be related to AR protein degradation in PC stem cells, revealed that MDM2 was responsible for the acquisition of antiandrogen resistance in LNCaP spheroids, which was overcome by KCa1.1 inhibition. Furthermore, a member of the multidrug resistance-associated protein subfamily of ABC transporters, MRP5 was responsible for the acquisition of DOX resistance in LNCaP spheroids, which was also overcome by KCa1.1 inhibition. Collectively, the present results suggest the potential of KCa1.1 in LNCaP spheroids, which mimic PC stem cells, as a therapeutic target for overcoming antiandrogen- and DOX-resistance in PC cells. Full article
(This article belongs to the Special Issue Pharmacology of Potassium Channels)
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