Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult-type nicotinic receptor channels

2002 ◽  
Vol 26 (4) ◽  
pp. 539-545 ◽  
Author(s):  
Bahram Mohammadi ◽  
Nicolas Lang ◽  
Reinhard Dengler ◽  
Johannes Bufler
Keyword(s):  
Skeletal Muscle ◽  
Sodium Channels ◽  
Nicotinic Receptor ◽  
Adult Type ◽  
High Concentrations ◽  
Nicotinic Receptor Channels

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.

scholarly journals ω-agatoxin IVA blocks nicotinic receptor channels in bovine chromaffin cells

FEBS Letters ◽  
1995 ◽  
Vol 362 (1) ◽  
pp. 15-18 ◽  
Author(s):  
Ricardo Granja ◽  
JoséM Fernández-Fernández ◽  
Victor Izaguirre ◽  
Carmen González-García ◽  
Valentin Ceña
Keyword(s):  
Nicotinic Receptor ◽  
Chromaffin Cells ◽  
Bovine Chromaffin Cells ◽  
Nicotinic Receptor Channels

scholarly journals Design of a Specific Activator for Skeletal Muscle Sodium Channels Uncovers Channel Architecture

2007 ◽  
Vol 282 (40) ◽  
pp. 29424-29430 ◽  
Author(s):  
Lior Cohen ◽  
Nitza Ilan ◽  
Maya Gur ◽  
Walter Stühmer ◽  
Dalia Gordon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sodium Channels ◽  
Channel Architecture

Mechanisms of Pi regulation of the skeletal muscle SR Ca2+ release channel

2000 ◽  
Vol 278 (3) ◽  
pp. C601-C611 ◽  
Author(s):  
Edward M. Balog ◽  
Bradley R. Fruen ◽  
Patricia K. Kane ◽  
Charles F. Louis
Keyword(s):  
Skeletal Muscle ◽  
Single Channel ◽  
Adenine Nucleotides ◽  
Muscle Fibers ◽  
Open Probability ◽  
Release Channel ◽  
High Concentrations ◽  
Channel Open Time ◽  
Stimulation Of

Inorganic phosphate (Pi) accumulates in the fibers of actively working muscle where it acts at various sites to modulate contraction. To characterize the role of Pi as a regulator of the sarcoplasmic reticulum (SR) calcium (Ca2+) release channel, we examined the action of Pi on purified SR Ca2+ release channels, isolated SR vesicles, and skinned skeletal muscle fibers. In single channel studies, addition of Pi to the cis chamber increased single channel open probability ( P o; 0.079 ± 0.020 in 0 Pi, 0.157 ± 0.034 in 20 mM Pi) by decreasing mean channel closed time; mean channel open times were unaffected. In contrast, the ATP analog, β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP), enhanced P o by increasing single channel open time and decreasing channel closed time. Pi stimulation of [3H]ryanodine binding by SR vesicles was similar at all concentrations of AMP-PCP, suggesting Pi and adenine nucleotides act via independent sites. In skinned muscle fibers, 40 mM Pi enhanced Ca2+-induced Ca2+ release, suggesting an in situ stimulation of the release channel by high concentrations of Pi. Our results support the hypothesis that Pi may be an important endogenous modulator of the skeletal muscle SR Ca2+ release channel under fatiguing conditions in vivo, acting via a mechanism distinct from adenine nucleotides.

Tetrodotoxin-insensitive sodium channels in a cardiac cell line from a transgenic mouse

1992 ◽  
Vol 262 (3) ◽  
pp. C724-C730 ◽  
Author(s):  
A. Sculptoreanu ◽  
M. Morton ◽  
C. L. Gartside ◽  
S. D. Hauschka ◽  
W. A. Catterall ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Line ◽  
Transgenic Mouse ◽  
Sodium Channels ◽  
Sodium Current ◽  
Cardiac Cell ◽  
Dependent Protein Kinase ◽  
Electrophysiological Properties ◽  
Maximal Activation ◽  
Dependent Protein

The electrophysiological properties of a cardiac cell line (MCM1) originating from a transgenic mouse were characterized. The dominant current in these cells is a sodium current that is insensitive to concentrations of tetrodotoxin (TTX) up to 100 microM. It activates and inactivates rapidly with half-maximal activation at -40 mV and half-maximal inactivation at -79 mV. This sodium current is reduced by agents that increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and activate cAMP-dependent protein kinase including isoproterenol, 8-bromo-cAMP, and isobutylmethylxanthine. The phenylalkylamine desmethoxyverapamil blocks the TTX-insensitive sodium current in MCM1 cells in both tonic and use-dependent fashion. Membrane depolarization enhances this block. It is proposed that the TTX-insensitive sodium current in these cells may be similar in origin to the embryonic type of TTX-insensitive sodium current described in other cardiac and skeletal muscle preparations.

Lactate inhibits Ca2+-activated Ca2+-channel activity from skeletal muscle sarcoplasmic reticulum

1997 ◽  
Vol 82 (2) ◽  
pp. 447-452 ◽  
Author(s):  
Terence G. Favero ◽  
, Anthony C. Zable ◽  
, David Colter ◽  
Jonathan J. Abramson
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Single Channel ◽  
Channel Activity ◽  
Release Channel ◽  
Muscle Lactate ◽  
Tension Development ◽  
Contraction Coupling ◽  
Single Channel Activity ◽  
High Concentrations

Favero, Terence G., Anthony C. Zable, David Colter, and Jonathan J. Abramson. Lactate inhibits Ca2+-activated Ca2+-channel activity from skeletal muscle sarcoplasmic reticulum. J. Appl. Physiol. 82(2): 447–452, 1997.—Sarcoplasmic reticulum (SR) Ca2+-release channel function is modified by ligands that are generated during about of exercise. We have examined the effects of lactate on Ca2+- and caffeine-stimulated Ca2+ release, [3H]ryanodine binding, and single Ca2+-release channel activity of SR isolated from rabbit white skeletal muscle. Lactate, at concentrations from 10 to 30 mM, inhibited Ca2+- and caffeine-stimulated [3H]ryanodine binding to and inhibited Ca2+- and caffeine-stimulated Ca2+ release from SR vesicles. Lactate also inhibited caffeine activation of single-channel activity in bilayer reconstitution experiments. These findings suggest that intense muscle activity, which generates high concentrations of lactate, will disrupt excitation-contraction coupling. This may lead to decreases in Ca2+ transients promoting a decline in tension development and contribute to muscle fatigue.

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