scholarly journals Nicotinic receptor-associated modulation of stimulatory and inhibitory neurotransmitters in NNK-induced adenocarcinoma of the lungs and pancreas

2009 ◽  
Vol 218 (4) ◽  
pp. 437-445 ◽  
Author(s):  
Hussein AN Al-Wadei ◽  
Hildegard M Schuller
Keyword(s):  
Nicotinic Receptor ◽  
Inhibitory Neurotransmitters

Receptor Binding Thermodynamics at the Neuronal Nicotinic Receptor

2004 ◽  
Vol 4 (3) ◽  
pp. 361-368 ◽  
Author(s):  
P.A. Borea ◽  
K. Varani ◽  
S.G., S. Merighi ◽  
A.D. Piaz ◽  
P. Gilli ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Nicotinic Receptor ◽  
Neuronal Nicotinic Receptor ◽  
Binding Thermodynamics

Prefrontal cortex nicotinic receptor inhibition by methyllycaconitine impaired cocaine-associated memory acquisition and retrieval

2021 ◽  
pp. 113212
Author(s):  
Verónica Pastor ◽  
Fernando Castillo Díaz ◽  
Valeria C. Sanabria ◽  
Juliana F. Dalto ◽  
Marta C. Antonelli ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nicotinic Receptor ◽  
Receptor Inhibition ◽  
Memory Acquisition

The Nicotinic Receptor Genes

1991 ◽  
Vol 14 ◽  
pp. S45-S61 ◽  
Author(s):  
S. Heinemann ◽  
J. Boulter ◽  
J. Connolly ◽  
E. Deneris ◽  
R. Duvoisin ◽  
...  
Keyword(s):  
Nicotinic Receptor

scholarly journals Desensitization Contributes to the Synaptic Response of Gain-of-Function Mutants of the Muscle Nicotinic Receptor

2006 ◽  
Vol 128 (5) ◽  
pp. 615-627 ◽  
Author(s):  
Sergio Elenes ◽  
Ying Ni ◽  
Gisela D. Cymes ◽  
Claudio Grosman
Keyword(s):  
Nicotinic Receptor ◽  
Dissociation Rate ◽  
Gain Of Function ◽  
Naturally Occurring ◽  
Channel Opening ◽  
Speed Up ◽  
High Concentrations ◽  
Dissociation Rate Constants ◽  
Kinetics Of ◽  
Peak Value

Although the muscle nicotinic receptor (AChR) desensitizes almost completely in the steady presence of high concentrations of acetylcholine (ACh), it is well established that AChRs do not accumulate in desensitized states under normal physiological conditions of neurotransmitter release and clearance. Quantitative considerations in the framework of plausible kinetic schemes, however, lead us to predict that mutations that speed up channel opening, slow down channel closure, and/or slow down the dissociation of neurotransmitter (i.e., gain-of-function mutations) increase the extent to which AChRs desensitize upon ACh removal. In this paper, we confirm this prediction by applying high-frequency trains of brief (∼1 ms) ACh pulses to outside-out membrane patches expressing either lab-engineered or naturally occurring (disease-causing) gain-of-function mutants. Entry into desensitization was evident in our experiments as a frequency-dependent depression in the peak value of succesive macroscopic current responses, in a manner that is remarkably consistent with the theoretical expectation. We conclude that the comparatively small depression of the macroscopic currents observed upon repetitive stimulation of the wild-type AChR is due, not to desensitization being exceedingly slow but, rather, to the particular balance between gating, entry into desensitization, and ACh dissociation rate constants. Disruption of this fine balance by, for example, mutations can lead to enhanced desensitization even if the kinetics of entry into, and recovery from, desensitization themselves are not affected. It follows that accounting for the (usually overlooked) desensitization phenomenon is essential for the correct interpretation of mutagenesis-driven structure–function relationships and for the understanding of pathological synaptic transmission at the vertebrate neuromuscular junction.

Sign in / Sign up

Export Citation Format

Share Document