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Muscle Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Kourosh Rezania, Peter Pytel, Betty Soliven
Mutations of the skeletal muscle Na+ channel gene SCN4A produce a spectrum of disorders characterized by myotonia and periodic paralysis, depending on the magnitude of membrane depolarization.50, 51 Mild membrane depolarization (5–10 mV) causes repetitive firing of action potentials (myotonia), while strong depolarization (20–30 mV) causes inactivation of Na+ channels and electrical silence (paralysis). Functional defects in mutant Na channels cause impaired inactivation and abnormal voltage dependence.
Neuro–Endocrine–Immune Dysfunction in the Chronic Pain Patient
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Local inhibitory pathways are interesting in that, over time, an inhibitory pathway can become excitatory and create a positive feedback loop. At baseline, there is a normal Cl− gradient with Cl− concentrations higher outside of the neuron than inside the neuron. This is established by the action of an active Cl− transporter pushing Cl− out of the cell. Typically, GABAA and glycine receptors are inhibitory secondary to their function as a Cl− ionophore and allow the influx of Cl− into the cell according to its gradient—diminishing the chance of a successful action potential. There are two receptor sites on GABA receptors. The active site binds GABA, muscimol, gaboxadol, and bicuculine, while drugs such as benzodiazepines, alcohol, and barbiturates bind to different allosteric binding sites. After nerve injury, the Cl− transporter activity becomes diminished. As a result, the Cl− concentration becomes reversed with higher concentrations of Cl− inside of the neuron. Now, these ionophore receptors result in membrane depolarization—improving the likelihood of a successful action potential.
The Cell Membrane in the Steady State
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The change in membrane conductance could be caused by: Physical stimuli, such as mechanical deformation, as in touch receptors and muscle receptors, or light in the case of photoreceptors.Chemical stimuli, as in taste and smell receptors as well as in nerve and muscle cells, whereby the binding of ligands to specific receptors on the outer or inner surface of the membrane change membrane conductance.Membrane depolarization, which affects membrane conductances in a specific manner, as discussed in the next chapter.
Solanaceae glycoalkaloids: α-solanine and α-chaconine modify the cardioinhibitory activity of verapamil
Published in Pharmaceutical Biology, 2022
Szymon Chowański, Magdalena Winkiel, Monika Szymczak-Cendlak, Paweł Marciniak, Dominika Mańczak, Karolina Walkowiak-Nowicka, Marta Spochacz, Sabino A. Bufo, Laura Scrano, Zbigniew Adamski
Calcium ions are crucial for the contraction of all types of muscles. After influx into the cytoplasm, they interact with myofilaments and ultimately allow for interaction between myosin and actin filaments, and thus for muscle contraction. Since they are a trigger and an executor of muscle contractions, their concentration in the sarcoplasm must be strictly regulated. In striated muscles, cell membrane depolarization is a signal that initiates the cascade responsible for muscle contraction. Changes in the cell membrane potential activate and open the L-type calcium channels. Then, the local increase in Ca2+ concentration activates the ryanodine receptor, a sarcoplasmic calcium channel, which releases the next portion of calcium ions into the cytoplasm, which interacts with myofilaments.
Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population
Published in Annals of Medicine, 2022
Mansour A. Alghamdi, Laith N. AL-Eitan, Ashwag Asiri, Doaa M. Rababa’h, Sultan A. Alqahtani, Mohammed S. Aldarami, Manar A. Alsaeedi, Raghad S. Almuidh, Abdulbari A. Alzahrani, Ahmad H. Sakah, Eman Mohamad El Nashar, Mansour Y. Otaif, Nawal F. Abdel Ghaffar
Epilepsy is a complex neurological condition that impacts the brain and cause seizure [24]. Genetic predisposition to epilepsy has been a fundamental part of the disorder aetiology [25]. Voltage-gated sodium channels are critical for genetics epilepsy, and these channels play a key role in mediating the electrical excitability. Thus, it is lucid that any genetic mutations in these gene coding channels can interfere the epilepsy development or progression. When the channels are activated by membrane depolarization, it will cause conformational change that increases the sodium ion influx in addition to cell depolarization and later the channels will be deactivated ending in resting of membrane potential [11]. This study investigated several genetic variants of SCN genes (SCN1A, SCN2A, SCN3A, SCN1B, SCN2B, SCN3B and SCN8A) and their association with epilepsy risk; these genes have been studied in this regard and conflicted results were reported [7]. rs3812718 is a common intronic variant that located in splice donor site, and it modifies alternative splicing of exon 5. We suggest that TT genotype of rs3812718 in SCN1A may be a protective factor against epilepsy and may decrease the risk of the disease in Saudi population. In contrast to our finding, rs3812718 was reported as a risk factor for GEFS + in Chinese population [26,27]. In one meta-analysis they revealed that the rs3812718 TT genotype was involved in high risk of developing drug resistance in epilepsy children [28].
Approaches for the discovery of drugs that target K Na 1.1 channels in KCNT1-associated epilepsy
Published in Expert Opinion on Drug Discovery, 2022
Barbara Miziak, Stanisław J Czuczwar
When membrane depolarization is persistently present, due to various inactivating mechanisms (e.g. slow cessation of transmission upon activation), the channels go into a non-conducting state. It is important to remember that inactivation is not the same as the reverse process of activation. In inactivation, the stimuli that activate the channel are still present, but the channels no longer conduct ions efficiently [39]. N-type inactivation binds to the intracellular region at the amino-terminal acting, resulting in pore closure. The entire process occurs within a few milliseconds. In case of C-type inactivation, it has been shown to be voltage independent over a range of −25 to +50 mV, and is partially coupled to N-type inactivation. Furthermore, the kinetics of this type of inactivation will vary depending on the alternatively spliced carboxy-terminal regions in the channels involved [40]. C-type inactivation has been shown to play an important role in modulating the firing of action potentials in neurons and cardiac muscle by regulating the availability of functional Kv channels [41].