Amitriptyline has a dual effect on the conductive properties of the epithelial Na channel

Pena, Florentina; Neaga, Emil; Amuzescu, Bogdan; Nitu, Alina; Flonta, Maria-Luiza

doi:10.1211/002235702760345482

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…The power‐law is the hallmark of ‘noise’ in physical systems, a fact that may be relevant to headache, which is increasingly being characterized as a modulation problem. The power‐law is ubiquitous, seen in physical systems of all sizes; from earthquakes and fluctuations of the Nile to heart rate, EEG and ion channel fluctuations 129‐137 . Channel noise is thought to arise from the random opening and closing of the channels in the cell membrane; a possible mechanism for it is variations in potassium conductance caused by vibration of hydrocarbon chains in neuronal membrane lipids 138 .…”

Section: A Pathology‐free Alternative—noise In the Trigeminovascular mentioning

confidence: 99%

“…The power-law is ubiquitous, seen in physical systems of all sizes; from earthquakes and fluctuations of the Nile to heart rate, EEG and ion channel fluctuations. [129][130][131][132][133][134][135][136][137] Channel noise is thought to arise from the random opening and closing of the channels in the cell membrane; a possible mechanism for it is variations in potassium conductance caused by vibration of hydrocarbon chains in neuronal membrane lipids. 138 Most of these phenomena are regarded as a form of random fluctuation called "1/f noise."…”

Section: A Pathology-free Alternative-noise In the Trigeminovascular mentioning

confidence: 99%

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The Lack of Peripheral Pathology in Migraine Headache

Lambert

2010

Headache

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This article reviews the baffling problem of the pathophysiology behind a peripheral genesis of migraine pain--or more particularly the baffling problem of its absence. I examine a number of pathophysiological states and the effector mechanisms for these states and find most of them very plausible and that they are all supported by abundant evidence. However, this evidence is mostly indirect; to date the occurrence of any of the presumed pathological states has not been convincingly demonstrated. Furthermore, there is little evidence of increased trigeminal sensory traffic into the central nervous system during a migraine attack. The article also examines a number of observations and experimental programs used to bolster a theory of peripheral pathology and suggests reasons why they may in fact not bolster it. I suggest that a pathology, if one exists, may be in the brain and even that it may not be a pathology at all. Migraine headache might just happen because of random noise in an exquisitely sensitive and complex network. The article suggests an experimental program to resolve these issues.

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Section: A Pathology‐free Alternative—noise In the Trigeminovascular mentioning

confidence: 99%

Section: A Pathology-free Alternative-noise In the Trigeminovascular mentioning

confidence: 99%

The Lack of Peripheral Pathology in Migraine Headache

Lambert

2010

Headache

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“…This stage of researchdevelopment, which involves a relatively small number of cells, is imperative to understand the variables described as the intermediate stage in the realization of artificial organs with a high number of cells, such as in the case of the kidney. In this case, there are extremely complex signaling mechanisms at the level of ion channels [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87] (which must be individually identified at the initial stage) and ion pumps, which require a multitude of cell types.…”

Section: Printing Of a Liver Tissue With Functional Cellular Asymmetrymentioning

confidence: 99%

Perspectives on Scaffold Designs with Roles in Liver Cell Asymmetry and Medical and Industrial Applications by Using a New Type of Specialized 3D Bioprinter

Harbuz,

Banciu,

David

et al. 2023

IJMS

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Cellular asymmetry is an important element of efficiency in the compartmentalization of intracellular chemical reactions that ensure efficient tissue function. Improving the current 3D printing methods by using cellular asymmetry is essential in producing complex tissues and organs such as the liver. The use of cell spots containing at least two cells and basement membrane-like bio support materials allows cells to be tethered at two points on the basement membrane and with another cell in order to maintain cell asymmetry. Our model is a new type of 3D bioprinter that uses oriented multicellular complexes with cellular asymmetry. This novel approach is necessary to replace the sequential and slow processes of organogenesis with rapid methods of growth and 3D organ printing. The use of the extracellular matrix in the process of bioprinting with cells allows one to preserve the cellular asymmetry in the 3D printing process and thus preserve the compartmentalization of biological processes and metabolic efficiency.

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“…21,37,38 Amitriptyline, a classical tricyclic antidepressant, has been long used for its analgesic effect. Using the fluctuation analysis technique in epithelia, we have evidenced two distinct dose-dependent actions of amitriptyline on native ENaC channels: 39 a decrease in unitary current amplitude and in amiloride binding rate. These findings led us to hypothesize an interference of this tricyclic tertiary amine with the binding of the pirazine ring of amiloride to the high affinity site located in the outer vestibule of ENaC.…”

Section: Introductionmentioning

confidence: 99%

ASIC1a activation by amitriptyline and FMRF-amide is removed by serine proteases

Marin¹,

Prica²,

Amuzescu³

et al. 2008

Channels

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Analgesia induced by certain tricyclic antidepressants has been largely used for decades, yet the mechanisms involved are incompletely understood. Starting from previously reported dual effects of amitriptyline on wild-type ENaC (see ref. 39), we extended our study to ASIC1a by performing a series of whole cell and singlechannel recordings of proton-activated currents in HEK293 cells. Acid pulses were applied at 2 or 5 min intervals, and amitriptyline (1-500 μM) was applied at a holding pH of 7.4 or 8.4 between pulses. Dose-response plots were fitted with dual Hill type functions, yielding a half-activatory constant of 0.3 μM and a half-inhibitory constant of 382 μM at pH 7.4. At pH 8.4 both constants were shifted to higher values (0.5 and 444 μM, respectively). In whole-cell experiments, FMRF-amide increased the peak amplitude of ASIC1a transients at 0.1 μM and decreased it at 1 and 100 μM. Single-channel recordings were idealized and fitted using an 8-state linear connectivity model comprising four consecutive activation steps. Both amitriptyline (1 μM) and FMRF-amide (0.1 μM) increased the unitary current amplitude, and modified the opening and closing rates of the first gating mode. They also increased the transition rate from the second to the first gating mode, and the rate of final closure. The activatory effect of both compounds vanished after a mild trypsin pretreatment, suggesting the existence of activatory sites for FMRF-amide and amitriptyline in the outer vestibule of ASIC1a, which can be removed by exo-or endogenous serine-proteases.

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Amitriptyline has a dual effect on the conductive properties of the epithelial Na channel

Cited by 5 publications

References 47 publications

The Lack of Peripheral Pathology in Migraine Headache

The Lack of Peripheral Pathology in Migraine Headache

Perspectives on Scaffold Designs with Roles in Liver Cell Asymmetry and Medical and Industrial Applications by Using a New Type of Specialized 3D Bioprinter

ASIC1a activation by amitriptyline and FMRF-amide is removed by serine proteases

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