ArticleThe Journal of physiology2011
Relaxation gating of the acetylcholine-activated inward rectifier K+ current is mediated by intrinsic voltage sensitivity of the muscarinic receptor.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 35 citations in OpenAlex.
- Charge Movements and Conformational Changes: Biophysical Properties and Physiology of Voltage-Dependent GPCRs.Biomolecules · 2024Review
- Voltage Sensors Embedded in G Protein-Coupled Receptors.International journal of molecular sciences · 2024Review
- In situ monolayer patch clamp of acutely stimulated human iPSC-derived cardiomyocytes promotes consistent electrophysiological responses to SK channel inhibition.Scientific reports · 2024Article
- Functional consequences of a rare human serotonergic 5-HTFrontiers in pharmacology · 2023Article
- G Protein-Coupled Receptors Regulated by Membrane Potential.International journal of molecular sciences · 2022Review
- The activity of the serotonergic 5-HTThe Journal of biological chemistry · 2022Article
- The role of M3 receptors in regulation of electrical activity deteriorates in the rat heart during ageing.Current research in physiology · 2022Article
- Voltage dependence of the cannabinoid CB1 receptor.Frontiers in pharmacology · 2022Article
- Differential voltage-dependent modulation of the ACh-gated K+ current by adenosine and acetylcholine.PloS one · 2022Article
- Voltage-Dependent Dopamine Potency at DFrontiers in pharmacology · 2020Article
- The voltage-sensitive cardiac MPflugers Archiv : European journal of physiology · 2018Article
- Modeling effects of voltage dependent properties of the cardiac muscarinic receptor on human sinus node function.PLoS computational biology · 2018Article
- Structural determinants at the M2 muscarinic receptor modulate the RGS4-GIRK response to pilocarpine by impairment of the receptor voltage sensitivity.Scientific reports · 2017Article
- M3 cholinoreceptors alter electrical activity of rat left atrium via suppression of L-type CaJournal of physiology and biochemistry · 2017Article
- The agonist-specific voltage dependence of M2 muscarinic receptors modulates the deactivation of the acetylcholine-gated K(+) current (I KACh).Pflugers Archiv : European journal of physiology · 2016Article
- Membrane Potential Controls the Efficacy of Catecholamine-induced β1-Adrenoceptor Activity.The Journal of biological chemistry · 2015Article
- RGS4 regulates partial agonism of the M2 muscarinic receptor-activated K+ currents.The Journal of physiology · 2014Article
- Gold nanoparticle-spermidine complex blocks the inward rectifier potassium channel.American journal of cardiovascular disease · 2014Article
- Short-term desensitization of muscarinic K+ current in the heart.Biophysical journal · 2013Article
- Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.The Journal of physiology · 2013Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Normal heart rate variability is critically dependent upon the G-protein-coupled, acetylcholine (ACh)-activated inward rectifier K+ current, I(KACh). A unique feature of I(KACh) is the so-called ‘relaxation' gating property that contributes to increased current at hyperpolarized membrane potentials. I(KACh) relaxation refers to a slow decrease or increase in current magnitude with depolarization or hyperpolarization, respectively. The molecular mechanism underlying this perplexing gating behaviour remains unclear. Here, we consider a novel explanation for I(KACh) relaxation based upon the recent finding that G-protein-coupled receptors (GPCRs) are intrinsically voltage sensitive and that the muscarinic agonists acetylcholine (ACh) and pilocarpine (Pilo) manifest opposite voltage-dependent I(KACh) modulation. We show that Pilo activation of I(KACh) displays relaxation characteristics opposite to that of ACh. We explain the opposite effects of ACh and Pilo using Markov models of I(KACh) that incorporate ligand-specific, voltage-dependent parameters. Based on experimental and computational findings, we propose a novel molecular mechanism to describe the enigmatic relaxation gating process: I(KACh) relaxation represents a voltage-dependent change in agonist affinity as a consequence of a voltage-dependent conformational change in the muscarinic receptor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.