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Article ; Online: Molecular mechanisms of cholinergic neurotransmission in visceral smooth muscles with a focus on receptor-operated TRPC4 channel and impairment of gastrointestinal motility by general anaesthetics and anxiolytics.

Zholos, Alexander V / Melnyk, Mariia I / Dryn, Dariia O

2023 Volume 242, Page(s) 109776

Abstract: Acetylcholine is the primary excitatory neurotransmitter in visceral smooth muscles, wherein it binds to and activates two muscarinic receptors subtypes, ... ...

Abstract	Acetylcholine is the primary excitatory neurotransmitter in visceral smooth muscles, wherein it binds to and activates two muscarinic receptors subtypes, M
MeSH term(s)	Anti-Anxiety Agents/pharmacology ; Acetylcholine/metabolism ; Muscle, Smooth ; Receptors, Muscarinic/metabolism ; Ion Channels/metabolism ; Muscle Contraction ; Synaptic Transmission ; Anesthetics, General/pharmacology ; Cholinergic Agents/pharmacology ; Gastrointestinal Motility ; Receptor, Muscarinic M3/agonists ; Receptor, Muscarinic M3/metabolism
Chemical Substances	Anti-Anxiety Agents ; Acetylcholine (N9YNS0M02X) ; Receptors, Muscarinic ; Ion Channels ; Anesthetics, General ; Cholinergic Agents ; Receptor, Muscarinic M3
Language	English
Publishing date	2023-10-31
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2023.109776
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Article: General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain.

Zholos, Alexander V / Dryn, Dariia O / Melnyk, Mariia I

Frontiers in physiology

2023 Volume 14, Page(s) 1174655

Abstract: General anesthesia produces multiple side effects. Notably, it temporarily impairs gastrointestinal motility following surgery and causes the so-called postoperative ileus (POI), a multifactorial and complex condition that develops secondary to ... ...

Abstract	General anesthesia produces multiple side effects. Notably, it temporarily impairs gastrointestinal motility following surgery and causes the so-called postoperative ileus (POI), a multifactorial and complex condition that develops secondary to neuromuscular failure and mainly affects the small intestine. There are currently limited medication options for POI, reflecting a lack of comprehensive understanding of the mechanisms involved in this complex condition. Notably, although acetylcholine is one of the major neurotransmitters initiating excitation-contraction coupling in the gut, cholinergic stimulation by prokinetic drugs is not very efficient in case of POI. Acetylcholine when released from excitatory motoneurones of the enteric nervous system binds to and activates M2 and M3 types of muscarinic receptors in smooth muscle myocytes. Downstream of these G protein-coupled receptors, muscarinic cation TRPC4 channels act as the major focal point of receptor-mediated signal integration, causing membrane depolarisation accompanied by action potential discharge and calcium influx via L-type Ca
Language	English
Publishing date	2023-05-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1174655
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Article: Editorial: Temperature-dependent mechanisms of neuron functioning: Emerging concepts.

Korogod, Sergiy M / Tsagareli, Merab / Delmas, Patrick / Zholos, Alexander V

Frontiers in cellular neuroscience

2022 Volume 16, Page(s) 1009071

Language	English
Publishing date	2022-08-18
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.1009071
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Article ; Online: Pico145 inhibits TRPC4-mediated mI

Dryn, Dariia O / Melnyk, Mariia I / Bon, Robin S / Beech, David J / Zholos, Alexander V

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 168, Page(s) 115672

Abstract: In intestinal smooth muscle cells, receptor-operated TRPC4 are responsible for the majority of muscarinic receptor cation current ( ... ...

Abstract	In intestinal smooth muscle cells, receptor-operated TRPC4 are responsible for the majority of muscarinic receptor cation current (mI
MeSH term(s)	Animals ; Male ; Mice ; Carbachol/pharmacology ; Gastrointestinal Motility ; Myocytes, Smooth Muscle/metabolism ; Receptors, Muscarinic/metabolism ; TRPC Cation Channels/antagonists & inhibitors ; TRPC Cation Channels/metabolism
Chemical Substances	Carbachol (8Y164V895Y) ; Receptors, Muscarinic ; TRPC Cation Channels
Language	English
Publishing date	2023-10-17
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115672
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Article ; Online: Calcium-dependent modulation of BK

Soloviev, Anatoly / Ivanova, Irina / Sydorenko, Vadym / Sukhanova, Khrystyna / Melnyk, Mariia / Dryn, Dariia / Zholos, Alexander

Acta physiologica (Oxford, England)

2023 Volume 237, Issue 3, Page(s) e13922

Abstract: Aim: Gold nanoparticles are widely used for biomedical applications, but the precise molecular mechanism of their interaction with cellular structures is still unclear. Assuming that intracellular calcium fluctuations associated with surface plasmon- ... ...

Abstract	Aim: Gold nanoparticles are widely used for biomedical applications, but the precise molecular mechanism of their interaction with cellular structures is still unclear. Assuming that intracellular calcium fluctuations associated with surface plasmon-induced calcium entry could modulate the activity of potassium channels, we studied the effect of 5 nm gold nanoparticles on calcium-dependent potassium channels and associated calcium signaling in freshly isolated rat pulmonary artery smooth muscle cells and cultured hippocampal neurons. Methods: Outward potassium currents were recorded using patch-clamp techniques. Changes in intracellular calcium concentration were measured using the high affinity Ca Results: In pulmonary artery smooth muscle cells, plasmonic gold nanoparticles increased the amplitude of currents via large-conductance Ca Conclusion: We conclude that fluctuations in intracellular calcium can modulate plasmonic gold nanoparticles-induced gating of BK
MeSH term(s)	Animals ; Rats ; Calcium/metabolism ; Egtazic Acid ; Gold/pharmacology ; Hippocampus/drug effects ; Hippocampus/metabolism ; Metal Nanoparticles/therapeutic use ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Neurons/metabolism ; Potassium Channels/metabolism ; Pulmonary Artery/metabolism
Chemical Substances	Calcium (SY7Q814VUP) ; Egtazic Acid (526U7A2651) ; Gold (7440-57-5) ; Potassium Channels ; Kcnma1 protein, rat
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2218636-0
ISSN	1748-1716 ; 1748-1708
ISSN (online)	1748-1716
ISSN	1748-1708
DOI	10.1111/apha.13922
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Article ; Online: TRP Channels in Respiratory Pathophysiology: the Role of Oxidative, Chemical Irritant and Temperature Stimuli.

Zholos, Alexander V

Current neuropharmacology

2015 Volume 13, Issue 2, Page(s) 279–291

Abstract: There is rapidly growing evidence indicating multiple and important roles of Ca(2+)- permeable cation TRP channels in the airways, both under normal and disease conditions. The aim of this review was to summarize the current knowledge of TRP channels in ... ...

Abstract	There is rapidly growing evidence indicating multiple and important roles of Ca(2+)- permeable cation TRP channels in the airways, both under normal and disease conditions. The aim of this review was to summarize the current knowledge of TRP channels in sensing oxidative, chemical irritant and temperature stimuli by discussing expression and function of several TRP channels in relevant cell types within the respiratory tract, ranging from sensory neurons to airway smooth muscle and epithelial cells. Several of these channels, such as TRPM2, TRPM8, TRPA1 and TRPV1, are discussed in much detail to show that they perform diverse, and often overlapping or contributory, roles in airway hyperreactivity, inflammation, asthma, chronic obstructive pulmonary disease and other respiratory disorders. These include TRPM2 involvement in the disruption of the bronchial epithelial tight junctions during oxidative stress, important roles of TRPA1 and TRPV1 channels in airway inflammation, hyperresponsiveness, chronic cough, and hyperplasia of airway smooth muscles, as well as TRPM8 role in COPD and mucus hypersecretion. Thus, there is increasing evidence that TRP channels not only function as an integral part of the important endogenous protective mechanisms of the respiratory tract capable of detecting and ensuring proper physiological responses to various oxidative, chemical irritant and temperature stimuli, but that altered expression, activation and regulation of these channels may also contribute to the pathogenesis of respiratory diseases.
MeSH term(s)	Animals ; Humans ; Irritants/pharmacology ; Respiration Disorders/drug therapy ; Respiration Disorders/metabolism ; Respiration Disorders/physiopathology ; Temperature ; Transient Receptor Potential Channels/metabolism
Chemical Substances	Irritants ; Transient Receptor Potential Channels
Language	English
Publishing date	2015-08-25
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2192352-8
ISSN	1875-6190 ; 1570-159X
ISSN (online)	1875-6190
ISSN	1570-159X
DOI	10.2174/1570159x13666150331223118
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Article: TRPC5.

Zholos, Alexander V

Handbook of experimental pharmacology

2014 Volume 222, Page(s) 129–156

Abstract: Human canonical transient receptor potential channel 5 (TRPC5) has been cloned from the Xq23 region on chromosome X as a suspect in nonsyndromic mental retardation. TRPC5 is a Ca(2+)-permeable cation channel predominantly expressed in the CNS, including ... ...

Abstract	Human canonical transient receptor potential channel 5 (TRPC5) has been cloned from the Xq23 region on chromosome X as a suspect in nonsyndromic mental retardation. TRPC5 is a Ca(2+)-permeable cation channel predominantly expressed in the CNS, including the hippocampus, cerebellum, amygdala, sensory neurons, and retina. It also shows more restricted expression in the periphery, notably in the kidney and cardiovascular system. Homotetrameric TRPC5 channels are primarily activated by receptors coupled to Gq and phospholipase C and/or Gi proteins, but TRPC5 channels may also gate in a store-dependent manner, which requires other partner proteins such TRPC1, STIM1, and Orai1. There is an impressive array of other activators of TRPC5 channels, such as nitric oxide, lysophospholipids, sphingosine-1-phosphate, reduced thioredoxin, protons, lanthanides, and calcium, and many can cause its direct activation. Moreover, TRPC5 shows constitutive activity, and it is responsive to membrane stretch and cold. Thus, TRPC5 channels have significant potential for synergistic activation and may serve as an important focal point in Ca(2+) signalling and electrogenesis. Moreover, TRPC5 functions in partnership with about 60 proteins, including TRPC1, TRPC4, calmodulin, IP3 receptors, NHERF, NCS-1, junctate, stathmin 2, Ca(2+)-binding protein 1, caveolin, and SESTD1, while its desensitisation is mediated by both protein kinases A and C. TRPC5 has a distinct voltage dependence shared only with its closest relative, TRPC4. Its unique N-shaped activation curve underlined by intracellular Mg(2+) block seems to be perfectly "shaped" to trigger action potential discharge, but not to grossly interfere with the action potential shape. The range of biological functions of TRPC5 channels is also impressive, from neurotransmission to control of axon guidance and vascular smooth muscle cell migration and contractility. Recent studies of Trpc5 gene knockouts begin to uncover its roles in fear, anxiety, seizures, and cold sensing.
MeSH term(s)	Animals ; Cell Membrane Permeability ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Humans ; Ion Channel Gating ; Membrane Potentials ; Mice ; Mice, Knockout ; Phenotype ; Protein Conformation ; Signal Transduction ; Structure-Activity Relationship ; TRPC Cation Channels/chemistry ; TRPC Cation Channels/deficiency ; TRPC Cation Channels/genetics ; TRPC Cation Channels/metabolism
Chemical Substances	TRPC Cation Channels ; TRPC5 protein, human ; Trpc5 protein, mouse
Language	English
Publishing date	2014
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/978-3-642-54215-2_6
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Article ; Online: Bidirectional TRP/L Type Ca

Dryn, Dariia O / Melnyk, Mariia I / Melanaphy, Donal / Kizub, Igor V / Johnson, Christopher D / Zholos, Alexander V

Biomolecules

2023 Volume 13, Issue 5

Abstract: TRP channels are expressed both in vascular myocytes and endothelial cells, but knowledge of their operational mechanisms in vascular tissue is particularly limited. Here, we show for the first time the biphasic contractile reaction with relaxation ... ...

Abstract	TRP channels are expressed both in vascular myocytes and endothelial cells, but knowledge of their operational mechanisms in vascular tissue is particularly limited. Here, we show for the first time the biphasic contractile reaction with relaxation followed by a contraction in response to TRPV4 agonist, GSK1016790A, in a rat pulmonary artery preconstricted with phenylephrine. Similar responses were observed both with and without endothelium, and these were abolished by the TRPV4 selective blocker, HC067047, confirming the specific role of TRPV4 in vascular myocytes. Using selective blockers of BK
MeSH term(s)	Rats ; Animals ; TRPV Cation Channels ; Muscle, Smooth, Vascular ; Endothelial Cells ; Vasodilation
Chemical Substances	TRPV Cation Channels ; TRPV4 inhibitor HC067047 ; Trpv4 protein, rat
Language	English
Publishing date	2023-04-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom13050759
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Article ; Online: Pharmacology of transient receptor potential melastatin channels in the vasculature.

Zholos, Alexander

British journal of pharmacology

2010 Volume 159, Issue 8, Page(s) 1559–1571

Abstract: Mammalian transient receptor potential melastatin (TRPM) non-selective cation channels, the largest TRP subfamily, are widely expressed in excitable and non-excitable cells where they perform diverse functions ranging from detection of cold, taste, ... ...

Abstract	Mammalian transient receptor potential melastatin (TRPM) non-selective cation channels, the largest TRP subfamily, are widely expressed in excitable and non-excitable cells where they perform diverse functions ranging from detection of cold, taste, osmolarity, redox state and pH to control of Mg(2+) homeostasis and cell proliferation or death. Recently, TRPM gene expression has been identified in vascular smooth muscles with dominance of the TRPM8 channel. There has been in parallel considerable progress in decoding the functional roles of several TRPMs in the vasculature. This research on native cells is aided by the knowledge of the activation mechanisms and pharmacological properties of heterologously expressed TRPM subtypes. This paper summarizes the present state of knowledge of vascular TRPM channels and outlines several anticipated directions of future research in this area.
MeSH term(s)	Animals ; Blood Vessels/drug effects ; Blood Vessels/physiology ; Humans ; TRPM Cation Channels/drug effects
Chemical Substances	TRPM Cation Channels
Language	English
Publishing date	2010-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/j.1476-5381.2010.00649.x
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Article ; Online: TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling.

Storozhuk, Maksim V / Zholos, Alexander V

Current neuropharmacology

2017 Volume 16, Issue 2, Page(s) 137–150

Abstract: Background: Chronic pain is a significant clinical problem and a very complex pathophysiological phenomenon. There is growing evidence that targeting the endocannabinoid system may be a useful approach to pain alleviation. Classically, the system ... ...

Abstract	Background: Chronic pain is a significant clinical problem and a very complex pathophysiological phenomenon. There is growing evidence that targeting the endocannabinoid system may be a useful approach to pain alleviation. Classically, the system includes G protein-coupled receptors of the CB1 and CB2 subtypes and their endogenous ligands. More recently, several subtypes of the large superfamily of cation TRP channels have been coined as "ionotropic cannabinoid receptors", thus highlighting their role in cannabinoid signalling. Thus, the aim of this review was to explore the intimate connection between several "painful" TRP channels, endocannabinoids and nociceptive signalling. Methods: Research literature on this topic was critically reviewed allowing us not only summarize the existing evidence in this area of research, but also propose several possible cellular mechanisms linking nociceptive and cannabinoid signaling with TRP channels. Results: We begin with an overview of physiology of the endocannabinoid system and its major components, namely CB1 and CB2 G protein-coupled receptors, their two most studied endogenous ligands, anandamide and 2-AG, and several enzymes involved in endocannabinoid biosynthesis and degradation. The role of different endocannabinoids in the regulation of synaptic transmission is then discussed in detail. The connection between the endocannabinoid system and several TRP channels, especially TRPV1-4, TRPA1 and TRPM8, is then explored, while highlighting the role of these same channels in pain signalling. Conclusion: There is increasing evidence implicating several TRP subtypes not only as an integral part of the endocannabinoid system, but also as promising molecular targets for pain alleviation with the use of endo- and phytocannabinoids, especially when the function of these channels is upregulated under inflammatory conditions.
MeSH term(s)	Animals ; Chronic Pain/drug therapy ; Endocannabinoids/pharmacology ; Endocannabinoids/therapeutic use ; Humans ; Ligands ; Signal Transduction/drug effects ; TRPV Cation Channels/metabolism
Chemical Substances	Endocannabinoids ; Ligands ; TRPV Cation Channels
Language	English
Publishing date	2017-04-24
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2192352-8
ISSN	1875-6190 ; 1570-159X
ISSN (online)	1875-6190
ISSN	1570-159X
DOI	10.2174/1570159X15666170424120802
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