Photopharmacological approaches for dissecting potassium channel physiology

Häfner, Stephanie; Sandoz, Guillaume

doi:10.1016/j.coph.2021.12.005

Cited by 5 publications

(8 citation statements)

References 34 publications

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“…The activity of potassium channels can be locally modulated by voltage-gating, mechanical or light stimulus, and external ligands. In the last decade, advances in optogenetics and chemical biology of ion channels have powered numerous medical applications through local regulation of electrical activity in living cells with the ultimate goal of treating major life-threatening diseases ( Gradinaru et al, 2010 ; Häfner and Sandoz, 2022 ; Snyder, 2017 ; Montnach et al, 2022 ). Interestingly, recent studies indicate the spatial–temporal regulation of ion channel expression and membrane potential status is critical for landmarking pathological conditions such as cardiac arrhythmia, epilepsy, or various types of cancer ( Rosati and McKinnon, 2004 ; Lastraioli et al, 2015 ; Zsiros et al, 2009 ; Niemeyer et al, 2001 ; Biasiotta et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Macroscopic control of cell electrophysiology through ion channel expression

García-Navarrete

Avdovic

Pérez-García

et al. 2022

eLife

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Cells convert electrical signals into chemical outputs to facilitate the active transport of information across larger distances. This electrical-to-chemical conversion requires a tightly regulated expression of ion channels. Alterations of ion channel expression provide landmarks of numerous pathological diseases, such as cardiac arrhythmia, epilepsy, or cancer. Although the activity of ion channels can be locally regulated by external light or chemical stimulus, it remains challenging to coordinate the expression of ion channels on extended spatial-temporal scales. Here, we engineered yeast S. cerevisiae to read and convert chemical concentrations into a dynamic potassium channel expression. A synthetic dual-feedback circuit controls the expression of engineered potassium channels through phytohormones auxin and salicylate to produce a macroscopically coordinated pulses of the plasma membrane potential (PMP). Our study provides a compact experimental model to control electrical activity through gene expression in eukaryotic cell populations setting grounds for various cellular engineering, synthetic biology, and potential therapeutic applications.

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Section: Introductionmentioning

confidence: 99%

Macroscopic control of cell electrophysiology through ion channel expression

García-Navarrete

Avdovic

Pérez-García

et al. 2022

eLife

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“…The activity of potassium channels can be locally modulated by voltage-gating, mechanical or light stimulus, and external ligands. In the last decade, advances in optogenetics and chemical biology of ion channels have powered numerous medical applications through local regulation of electrical activity in living cells with the ultimate goal of treating major life-threatening diseases (7)(8)(9)(10). Interestingly, recent studies indicate the spatial-temporal regulation of ion channel expression is critical for landmarking pathological conditions such as cardiac arrhythmia, epilepsy, or various types of cancer (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Macroscopic control of synchronous electrical signaling with chemically-excited gene expression

Wabnik¹,

Navarrete²,

Avdovic³

et al. 2022

Preprint

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Excitable nerve cells convert electrical signals into chemical outputs to facilitate the active transport of information across the nervous system. We engineered unicellular microbe S. cerevisiae to directly read and convert local chemical concentrations into a dynamic electrical field that is uniformly distributed across fungi populations. The chemically-excitable dual-feedback gene circuit precisely tunes the expression of active potassium channels, coordinating cyclic firing of the plasma membrane potential (PMP). Our findings provide mechanistic insights into how cells transform local chemical environments into electrical signals to guide coordinated behavior at the macroscopic scale.

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“…These channels are composed of tetrameric integral membrane regions, which form an aqueous pore for K + to permeate across the membrane. This ion serves a critical role in maintaining electrical gradients during the repolarization of action potentials and maintaining the negative resting membrane potential [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, this segment is also protected during depolarization of the action potential (AP). This protection is due to the presence of the acidic residues on S1 and S2 transmembrane segments, which limits deterrence [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Within the family of Kv channels, there are subfamilies that can be grouped according to the N- and C-terminal domains and encoded genes [ 5 , 6 ]. The importance behind the subfamily grouping lies in the Kv proteins, which can be functionally divergent with different membrane sensitivity potentials, gating interactions, and dynamic responses [ 4 ]. These subfamilies of Kv channels are all encoded by 40 genes, and current literature establishes exactly 12 subfamilies of Kv channels as a product of this gene encoding (e.g., Kv1–12) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Behavior of KCNQ Channels in Neural Plasticity and Motor Disorders

et al. 2022

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The broad distribution of voltage-gated potassium channels (VGKCs) in the human body makes them a critical component for the study of physiological and pathological function. Within the KCNQ family of VGKCs, these aqueous conduits serve an array of critical roles in homeostasis, especially in neural tissue. Moreover, the greater emphasis on genomic identification in the past century has led to a growth in literature on the role of the ion channels in pathological disease as well. Despite this, there is a need to consolidate the updated findings regarding both the pharmacotherapeutic and pathological roles of KCNQ channels, especially regarding neural plasticity and motor disorders which have the largest body of literature on this channel. Specifically, KCNQ channels serve a remarkable role in modulating the synaptic efficiency required to create appropriate plasticity in the brain. This role can serve as a foundation for clinical approaches to chronic pain. Additionally, KCNQ channels in motor disorders have been utilized as a direction for contemporary pharmacotherapeutic developments due to the muscarinic properties of this channel. The aim of this study is to provide a contemporary review of the behavior of these channels in neural plasticity and motor disorders. Upon review, the behavior of these channels is largely dependent on the physiological role that KCNQ modulatory factors (i.e., pharmacotherapeutic options) serve in pathological diseases.

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Photopharmacological approaches for dissecting potassium channel physiology

Cited by 5 publications

References 34 publications

Macroscopic control of cell electrophysiology through ion channel expression

Macroscopic control of cell electrophysiology through ion channel expression

Macroscopic control of synchronous electrical signaling with chemically-excited gene expression

Behavior of KCNQ Channels in Neural Plasticity and Motor Disorders

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