Hydrocortisone inhibition of wild‐type and αD200Q nicotinic acetylcholine receptors

Dworakowska, Beata; Nurowska, Ewa; Dołowy, Krzysztof

doi:10.1111/cbdd.13325

Cited by 6 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though it is necessary to perform more experiments to characterize in detail the polyamine-induced blocking mechanism that generates the 'reopening current', we propose that the phenomenon of a 'reopening current' is consistent with the mechanism proposed recently for blocking of the nACh receptor by hydrocortisone [17]. It was suggested that hydrocortisone was able to displace an agonist from its binding site.…”

Section: Discussionsupporting

confidence: 84%

Effect of polyamines on the nicotinic ACh receptor

Nurowska¹,

Tumiatti²,

Dworakowska³

2018

J Pre Clin Clin Res.

Self Cite

View full text Add to dashboard Cite

Introduction. In recent years, interactions of various polyamines with a number of ionotropic receptors have been reported. Such interactions can be either negative (inhibition) or positive (potentiation). It is proposed that hydrophilic polyamines act as open-channel blockers and bind sites deeply in the ion channel pore. Hydrophobic polyamines are believed to act in the shallower part of the pore. There has been cause to think that polyamines with two aromatic moieties block the nicotinic acetylcholine (nACh) receptor by adopting a U-shaped conformation, that is, a conformation in which the long positively charged polyamine chain enters the ion channel while aromatic moieties interact with extracellular parts of α-subunits. Objective. Our goal was to determine whether and how changes in the structure of methoctramine (a polyamine with two aromatic moieties) affect the way in which the nACh receptor is blocked. We synthesized derivatives of methoctramine which have a less flexible structure than methoctramine itself and may be less capable of adopting a U-shaped conformation within the ion channel. Materials and method. Whole-cell ACh-induced currents were recorded from mouse i28 satellite cells expanded in culture. Recordings were performed both in the presence and in the absence of polyamines. Results. All tested polyamines applied at a concentration of 5 mM blocked ACh-induced currents. Depending on the number of protonated nitrogen atoms, polyamines decreased the current amplitude and/or increased the decay rate of the current. Conclusions. We propose two possible mechanisms to explain the action of polyamines: desensitization, and displacement of agonist molecules from their binding sites. The impact of the number of protonated nitrogen atoms is discussed.

show abstract

Section: Discussionsupporting

confidence: 84%

Effect of polyamines on the nicotinic ACh receptor

Nurowska¹,

Tumiatti²,

Dworakowska³

2018

J Pre Clin Clin Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conceptually, antibodies to the AChR (anti-AChR) must be presented in the circulation prior to the development of neurophysiological manifestations in subclinical patients (14). A surge in circulating glucocorticoid levels in response to acute stress may exert a direct inhibitory action on the AChR, and therefore can precipitate myasthenic symptoms (15). Glucocorticoids may exert contradictory effects on immune system depending on their concentration.…”

Section: Discussionmentioning

confidence: 99%

Remission of myasthenia gravis following cervical adjustment

Chu¹,

Bellin²

2019

AME Case Rep

View full text Add to dashboard Cite

Myasthenia gravis (MG) is an autoimmune disorder, caused by circulating antibodies against the acetylcholine receptor (AChR) and associated proteins. Anticholinesterase medications and immunomodulating therapies are the mainstays of current treatment. Presented here is a case of a 51-yearold female who had been diagnosed with MG based on symptoms and continued elevation of antibody to AChR (anti-AChR) by her family physician. The patient's anticholinesterase medication was halted due to significant side effects affecting bowel function. She only received acupuncture treatment in the past 4 months prior to this presentation. Myasthenic symptoms deteriorated and the anti-AChR titer kept elevating after stopping medication. She originally came to us due to neck and back pain rather than myasthenic complaints. This case is interesting that her back pain and myasthenic symptoms went into complete remission within 1 month of initiating chiropractic adjustment. The concomitant recession of the myasthenic symptoms raises considerable interest for the mystery of MG, including the causal link between stress and autoimmune disease, the role of ACh in immune regulation, and the possible mechanisms of disease amelioration. Further studies would shed more light on the efficacy of various modalities in treating MG.

show abstract

“…The threshold of the opening transition was set at one-half of the unitary current. Open dwell times were calculated by fitting the probability density function (the sum of two exponential terms [ 45 ]) to open time histograms with the use of Clampfit. τ oi corresponds to the time constant of the i th component, P corresponds to its normalized area.…”

Section: Methodsmentioning

confidence: 99%

Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium

Dworakowska

Gawlak

Nurowska

2021

Biology

Self Cite

View full text Add to dashboard Cite

TREK-2-like channels in the pyramidal neurons of rat prefrontal cortex are characterized by a wide range of spontaneous activity—from very low to very high—independent of the membrane potential and the stimuli that are known to activate TREK-2 channels, such as temperature or membrane stretching. The aim of this study was to discover what factors are involved in high levels of TREK-2-like channel activity in these cells. Our research focused on the PI(4,5)P2-dependent mechanism of channel activity. Single-channel patch clamp recordings were performed on freshly dissociated pyramidal neurons of rat prefrontal cortexes in both the cell-attached and inside-out configurations. To evaluate the role of endogenous stimulants, the activity of the channels was recorded in the presence of a PI(4,5)P2 analogue (PI(4,5)P2DiC8) and Ca2+. Our research revealed that calcium ions are an important factor affecting TREK-2-like channel activity and kinetics. The observation that calcium participates in the activation of TREK-2-like channels is a new finding. We showed that PI(4,5)P2-dependent TREK-2 activity occurs when the conditions for PI(4,5)P2/Ca2+ nanocluster formation are met. We present a possible model explaining the mechanism of calcium action.

show abstract

Hydrocortisone inhibition of wild‐type and αD200Q nicotinic acetylcholine receptors

Cited by 6 publications

References 35 publications

Effect of polyamines on the nicotinic ACh receptor

Effect of polyamines on the nicotinic ACh receptor

Remission of myasthenia gravis following cervical adjustment

Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium

Contact Info

Product

Resources

About