Regulation of neural ion channels by muscarinic receptors

Brown, David A.

doi:10.1016/j.neuropharm.2017.11.024

Cited by 32 publications

(31 citation statements)

References 228 publications

(243 reference statements)

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“…Like endocytosis, many ion channels and transporters in the plasma membrane also depend on the presence of PI(4,5)P 2 for correct functioning [112][113][114]. PI(4,5)P 2 acts directly on ion channels including inwardly rectifying K + (Kir) channels, KCNQ (also known as Kv) channels and transporters such as the Na + /Ca 2+ exchanger to facilitate their opening.…”

Section: Ion Channel Regulation By Pi(45)pmentioning

confidence: 99%

Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane

Katan

Cockcroft

2020

Essays in Biochemistry

115

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Phosphatidylinositol(4,5) bisphosphate (PI(4,5)P2) has become a major focus in biochemistry, cell biology and physiology owing to its diverse functions at the plasma membrane. As a result, the functions of PI(4,5)P2 can be explored in two separate and distinct roles – as a substrate for phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K) and as a primary messenger, each having unique properties. Thus PI(4,5)P2 makes contributions in both signal transduction and cellular processes including actin cytoskeleton dynamics, membrane dynamics and ion channel regulation. Signalling through plasma membrane G-protein coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and immune receptors all use PI(4,5)P2 as a substrate to make second messengers. Activation of PI3K generates PI(3,4,5)P3 (phosphatidylinositol(3,4,5)trisphosphate), a lipid that recruits a plethora of proteins with pleckstrin homology (PH) domains to the plasma membrane to regulate multiple aspects of cellular function. In contrast, PLC activation results in the hydrolysis of PI(4,5)P2 to generate the second messengers, diacylglycerol (DAG), an activator of protein kinase C and inositol(1,4,5)trisphosphate (IP3/I(1,4,5)P3) which facilitates an increase in intracellular Ca2+. Decreases in PI(4,5)P2 by PLC also impact on functions that are dependent on the intact lipid and therefore endocytosis, actin dynamics and ion channel regulation are subject to control. Spatial organisation of PI(4,5)P2 in nanodomains at the membrane allows for these multiple processes to occur concurrently.

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Section: Ion Channel Regulation By Pi(45)pmentioning

confidence: 99%

Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane

Katan

Cockcroft

2020

Essays in Biochemistry

115

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“…These receptors may be broadly divided in two categories, based on their Gprotein coupling activity (D. A. Brown, 2018;Kruse, et al, 2014;Zenko & Hislop, 2018). The M1R, M3R and M5R are coupled to G q -type proteins and activate phospholipase C to recruit phosphoinositol triphosphate-signaling cascade.…”

Section: Muscarinic Receptorsmentioning

confidence: 99%

Acetylcholine signaling system in progression of lung cancers

Friedman

Richbart

Merritt

et al. 2019

Pharmacology & Therapeutics

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The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyltransferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetylcholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic receptors on lung cancer cells to accelerate their proliferation, migration and invasion. Out of all components of the cholinergic pathway, the nAChR-signaling has been studied the most intensely. The reason for this trend is due to genome-wide data studies showing that nicotinic receptor subtypes are involved in lung cancer risk, the relationship between cigarette smoke and lung cancer risk as well as the rising popularity of electronic cigarettes considered by many as a "safe" alternative to smoking. There are a small number of review articles which review the contribution of the other cholinergic proteins in the pathophysiology of lung cancer. The primary objective of this review article is to discuss the function of the acetylcholine-signaling proteins in the progression of lung cancer. The investigation of the role of cholinergic network in lung cancer will pave the way to novel molecular targets and drugs in this lethal malignancy.

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“…Memory performance is part of a complex and interrelated system involving many cellular and molecular mechanisms [16]. Activation of TRPM2 causes Ca 2+ entry along the plasma membrane and Ca 2+ release from lysosomes [59], whereas activation of CHRMs changes the activity of membrane ion channels [60]. We evaluated TRPM2 and CHRM1 activities together because of these similar activities and since both were associated with ischemia reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

The decrease in hippocampal transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) is associated with memory loss in a surgical menopause rat model

et al. 2021

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The aim of the study was to investigate the association of transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) activity with the memorial functions that are deteriorated in surgical menopause. Material and methods: A total of 14 female rats were randomly divided into 2 groups: group (G)1: sham group; group (G)2: surgical menopause group, the group in which bilateral ovariectomy was performed. Fourteen days after the surgical procedure, learning and memorial tests were performed in G1 and G2 for a totally 13 days. The time required for the rats to find the cheese in the labyrinth was recorded and statistical evaluation of it was performed between groups. On the 14 th day of the memory test, the rats were decapitated and the brain tissues were fixed in 10% formalin. Hippocampal TRPM2 and CHRM1 gene expression was evaluated with RNA isolation, complementary DNA (cDNA) synthesis and quantitative real-time PCR (qRT-PCR) analysis. TRPM2 and CHRM1 immunoreactivity was evaluated in hippocampal tissue with the immunohistochemical method. Histo-score was calculated regarding the diffuseness of and severity of the staining; and statistical analyses were performed. Results: In the ovariectomized group, the mean time required for the rats to find the cheese was statistically significantly elongated (39.29 ±4.0 s vs. 29.86 ±2.6 s). When the hippocampal TRPM2 and CHRM1 gene expression and immunoreactivity were compared with the sham group, there was a statistically significant decrease in the surgical menopause group (p < 0.05). Conclusions: In surgical menopause, in deterioration of memorial functions, hippocampal TRPM2 channel and CHRM1 activity plays an important role.

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Regulation of neural ion channels by muscarinic receptors

Cited by 32 publications

References 228 publications

Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane

Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane

Acetylcholine signaling system in progression of lung cancers

The decrease in hippocampal transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) is associated with memory loss in a surgical menopause rat model

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