Sertraline is a commonly used antidepressant of the selective serotonin reuptake inhibitors (SSRIs) class. In this study, we have used the patch-clamp technique to assess the effects of sertraline on Kv2.1 channels heterologously expressed in HEK-293 cells and on the voltage-gated potassium currents (I) of Neuro 2a cells, which are predominantly mediated by Kv2.1 channels. Our results reveal that sertraline inhibits Kv2.1 channels in a concentration-dependent manner. The sertraline-induced inhibition was not voltage-dependent and did not require the channels to be open. The kinetics of activation and deactivation were accelerated and decelerated, respectively, by sertraline. Moreover, the inhibition by this drug was use-dependent. Notably, sertraline significantly modified the inactivation mechanism of Kv2.1 channels; the steady-state inactivation was shifted to hyperpolarized potentials, the closed-state inactivation was enhanced and accelerated, and the recovery from inactivation was slowed, suggesting that this is the main mechanism by which sertraline inhibits Kv2.1 channels. Overall, this study provides novel insights into the pharmacological actions of sertraline on Kv2.1 channels, shedding light on the intricate interaction between SSRIs and ion channel function.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2024.176487 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Kv2 channels do not function as canonical delayed rectifiers in spinal motoneurons.
iScience
August 2024
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
The increased muscular force output required for some behaviors is achieved via amplification of motoneuron output via cholinergic C-bouton synapses. Work in neonatal mouse motoneurons suggested that modulation of currents mediated by post-synaptically clustered K2.1 channels is crucial to C-bouton amplification.
View Article and Find Full Text PDFTherapeutic role of voltage-gated potassium channels in age-related neurodegenerative diseases.
Front Cell Neurosci
May 2024
Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Bilbao, Spain.
Article Synopsis
- - Voltage-gated ion channels are crucial for maintaining membrane potential and regulating electrical signals in neurons, with voltage-gated potassium channels (K) being particularly important for neuronal excitability.
- - High levels of reactive oxygen species (ROS) in the aging brain can impact K channels, contributing to aging and neurodegeneration, especially in conditions like Alzheimer's, Parkinson's, and Huntington's diseases.
- - The review highlights specific K channels affected in these disorders (K1, K2.1, K3, K4, K7) and suggests that modulators of these channels may serve as potential therapeutic targets to prevent or treat neurodegenerative diseases.
Altered neurological and neurobehavioral phenotypes in a mouse model of the recurrent KCNB1-p.R306C voltage-sensor variant.
Neurobiol Dis
May 2024
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Northwestern University Interdepartmental Neuroscience Program, Northwestern University, Chicago, IL 60611, USA. Electronic address:
Pathogenic variants in KCNB1 are associated with a neurodevelopmental disorder spectrum that includes global developmental delays, cognitive impairment, abnormal electroencephalogram (EEG) patterns, and epilepsy with variable age of onset and severity. Additionally, there are prominent behavioral disturbances, including hyperactivity, aggression, and features of autism spectrum disorder. The most frequently identified recurrent variant is KCNB1-p.
View Article and Find Full Text PDFA computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle.
Elife
February 2024
Department of Physiology & Membrane Biology, University of California, Davis, Davis, United States.
The function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure. Here, we describe an in silico model, which we call the 'Hernandez-Hernandez model', of electrical and Ca signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular Ca signaling during the development of myogenic tone in arterial blood vessels.
View Article and Find Full Text PDFThe formation of K2.1 macro-clusters is required for sex-specific differences in L-type Ca1.2 clustering and function in arterial myocytes.
Commun Biol
November 2023
Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA.
Article Synopsis
- Voltage-gated Ca1.2 and K2.1 channels in arterial myocytes are essential for muscle contraction and relaxation; K2.1 also enhances Ca1.2 clustering specifically in females.
- Research shows that K2.1 can form small micro-clusters that grow into larger macro-clusters when a specific site (S590) is phosphorylated, with females exhibiting higher phosphorylation and clustering than males.
- Disruption of K2.1's clustering ability affects Ca1.2 cluster size and activity, suggesting that K2.1 clustering plays a crucial, sex-specific role in regulating Ca1.2 function in arterial myocytes.*
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!