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Dear Colleagues,

Ion channels on the cell membrane play a crucial role in the movement of varying ions in and out of cells and have a significant impact on the cell membrane potential. Particularly, when the cell membrane undergoes depolarization or hyperpolarization, it activates different voltage-gated ion channels with varying strengths and gating properties. These various forms of voltage-gated currents are regulated by numerous drugs, which in turn influence the discharge frequency and behavior of different cells, potentially impacting their functional activities. Recently, it has been observed that alongside having specific targets in the cytoplasm or cell nucleus, many drugs tend to reside on the cell membrane before entering the cell. It is highly likely that these drugs also interact with specific regulatory functions. Such interactions may directly or indirectly affect the original site of drug action and simultaneously influence the discharge behavior of excitable cells. Therefore, understanding the specific modulation of ion channels on the cell membrane by different drugs has become critically important. Additionally, it is necessary to elucidate the structural modifications of these specialized drugs and their potential mechanisms of action on ion channels. Thus, we hope to continue with the original Special Issue and invite interested researchers in this field to contribute their experimental findings and achievements by providing a platform for a fruitful exchange of ideas and discoveries.

Prof. Dr. Sheng-Nan Wu
Guest Editor

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Keywords

ion currents
current kinetics
gating properties
voltage-dependent hysteresis
frequency-dependent regulation
small-molecule modulator

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Review

12 pages, 899 KiB

Open AccessReview

Exploring the Impact of BK_Ca Channel Function in Cellular Membranes on Cardiac Electrical Activity

by Yin-Chia Chen, Chia-Lung Shih, Chao-Liang Wu, Yi-Hsien Fang, Edmund Cheung So and Sheng-Nan Wu

Int. J. Mol. Sci. 2024, 25(3), 1537; https://doi.org/10.3390/ijms25031537 - 26 Jan 2024

Viewed by 686

Abstract

This review paper delves into the current body of evidence, offering a thorough analysis of the impact of large-conductance Ca²⁺-activated K⁺ (BK_Ca or BK) channels on the electrical dynamics of the heart. Alterations in the activity of BK_Ca channels, responsible for the generation of the overall magnitude of Ca²⁺-activated K⁺ current at the whole-cell level, occur through allosteric mechanisms. The collaborative interplay between membrane depolarization and heightened intracellular Ca²⁺ ion concentrations collectively contribute to the activation of BK_Ca channels. Although fully developed mammalian cardiac cells do not exhibit functional expression of these ion channels, evidence suggests their presence in cardiac fibroblasts that surround and potentially establish close connections with neighboring cardiac cells. When cardiac cells form close associations with fibroblasts, the high single-ion conductance of these channels, approximately ranging from 150 to 250 pS, can result in the random depolarization of the adjacent cardiac cell membranes. While cardiac fibroblasts are typically electrically non-excitable, their prevalence within heart tissue increases, particularly in the context of aging myocardial infarction or atrial fibrillation. This augmented presence of BK_Ca channels’ conductance holds the potential to amplify the excitability of cardiac cell membranes through effective electrical coupling between fibroblasts and cardiomyocytes. In this scenario, this heightened excitability may contribute to the onset of cardiac arrhythmias. Moreover, it is worth noting that the substances influencing the activity of these BK_Ca channels might influence cardiac electrical activity as well. Taken together, the BK_Ca channel activity residing in cardiac fibroblasts may contribute to cardiac electrical function occurring in vivo. Full article

(This article belongs to the Special Issue Ion Channels as a Potential Target in Pharmaceutical Designs 2.0)

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