User:Yaqi Zhao/sandbox/Channelopathy/skeleton muscle

Channelopathy
Sodium channel, implicated in channelopathies including Brugada syndrome, Long QT syndrome, Dravet syndrome, Paramyotonia congenita
Specialty	Medical genetics, Neuromuscular medicine, Cardiology
Symptoms	Dependent on type. Include: Syncope, muscle weakness, seizures, breathlessness
Complications	Dependent on type. Include: Sudden death
Causes	Genetic variants

Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them. These diseases may be either congenital (often resulting from a mutation or mutations in the encoding genes) or acquired (often resulting from autoimmune attack on an ion channel).

There are many distinct dysfunctions known to be caused by ion channel mutations. The genes for the construction of ion channels are highly conserved amongst mammals and one condition, hyperkalemic periodic paralysis, was first identified in the descendants of Impressive, a registered Quarter Horse.

The channelopathies of human skeletal muscle include hyper- and hypokalemic (high and low potassium blood concentrations) periodic paralysis, myotonia congenita and paramyotonia congenita.

Channelopathies affecting synaptic function are a type of synaptopathy.

Types

The types in the following table are commonly accepted. Channelopathies currently under research, like Kir4.1 potassium channel in multiple sclerosis, are not included.

Condition	Channel type
Alternating hemiplegia of childhood	Na⁺/K⁺-ATPase
Bartter syndrome	various by type
Brugada syndrome	various, by type
Catecholaminergic polymorphic ventricular tachycardia (CPVT)	Ryanodine receptor
Congenital hyperinsulinism	Inward-rectifier potassium ion channel
Cystic fibrosis	Chloride channel
Dravet Syndrome	Voltage-gated sodium channel
Episodic Ataxia	Voltage-gated potassium channel
Erythromelalgia	Voltage-gated sodium channel
Generalized epilepsy with febrile seizures plus	Voltage-gated sodium channel
Familial hemiplegic migraine	various
Associated with one particular disabling form of Fibromyalgia	Voltage-gated sodium channel
Hyperkalemic periodic paralysis	Voltage-gated sodium channel
Hypokalemic periodic paralysis	Voltage-gated sodium channel or voltage-dependent calcium channel (calciumopathy)
Lambert-Eaton myasthenic syndrome	Voltage-gated calcium channel
Long QT syndrome main type Romano-Ward syndrome	various, by type
Malignant hyperthermia	Ligand-gated calcium channel
Mucolipidosis type IV	Non-selective cation channel
Myotonia congenita	Voltage-dependent chloride channel
Neuromyelitis optica	Aquaporin-4 water channel
Neuromyotonia	Voltage-gated potassium channel
Nonsyndromic deafness	various
Paramyotonia congenita (a periodic paralysis)	Voltage-gated sodium channel
Polymicrogyria (Brain Malformation)	Voltage-gated sodium channel, SCN3A ATP1A3
Retinitis pigmentosa (some forms)	Ligand-gated non-specific ion channels
Short QT syndrome	various potassium channels suspected
Timothy syndrome	Voltage-dependent calcium channel
Tinnitus	Voltage-gated potassium channel of the KCNQ family
Seizure	Voltage-dependent potassium channel

Bibliography

• Song YW, Kim SJ, Heo TH, Kim MH, Kim JB (December 2012). "Normokalemic periodic paralysis is not a distinct disease". Muscle & Nerve. 46 (6): 914–6. doi:10.1002/mus.23441. PMID 22926674. S2CID 43821573.

External links

VIDEO Channel Surfing in Pediatrics by Carl E. Stafstrom, M.D., at the UW-Madison Health Sciences Learning Center.

• "The Weiss Lab". The Weiss Lab is investigating the molecular and cellular mechanisms underlying human diseases caused by dysfunction of ion channels.
• The Channelopathy Foundation - Foundation for Ion Channel diseases
• Cystic Fibrosis Foundation
• Rare Diseases Clinical Research Network

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Above original article, edits below

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Channelopathy

Introduction

Channelopathies are a group of diseases caused by the dysfunction of ion channel subunits or their interacting proteins. These diseases can be inherited or acquired by other disorders, drugs, or toxins. Mutations in genes encoding ion channels, which impair channel function, are the most common cause of channelopathies. There are more than 400 genes that encode ion channels, found in all human cell types and are involved in almost all physiological processes. Each type of channel is a multimeric complex of subunits encoded by a number of genes. Depending where the mutation occurs it may affect the gating, conductance, ion selectivity, or signal transduction of the channel.

Channelopathies can be categorized based on the organ system which they are associated with. In the cardiovascular system, the electrical impulse needed for each heartbeat is made possible by the electrochemical gradient of each heart cell. Because the heartbeat is dependent on the proper movement of ions across the surface membrane, cardiac channelopathies make up a key group of heart diseases. Long QT syndrome, the most common form of cardiac channelopathy, is characterized by prolonged ventricular repolarization, predisposing to a high risk of ventricular tachyarrhythmias (e.g., torsade de pointes), syncope, and sudden cardiac death.

Skeleton muscle channelopathy

The channelopathies of human skeletal muscle are a series of rare gene disorder diseases include periodic paralyses and non-dystrophic myotonias based on clinical symptoms. The dysfunction of sarcolemmal ion channels result in the loss of skeletal muscle excitability to contract (muscle weakness), or to relax (myotonia). However, the diagnosis and therapy are challenged by the obscure symptoms and diverse phenotypic manifestations.

Periodic paralyses

Periodic paralyses are autosomal-dominant disorders of muscle excitability, which can be classified into hyperkalemic periodic paralyses, hypokalemic periodic paralyses, and Andersen-Tawil syndrome (ATS). They are caused by mutations of sodium (Na_v1.4), calcium (Ca_v1.1), and several inward-rectifier potassium channels (K_ir2.1, K_ir2.6, and K_ir3.4).

• Hyperkalemic periodic paralysis is induced by abnormal high serum K⁺ ions due to mutations of Na_v1.4. Na_v1.4 channel is inactivated, companied with sodium influx and cell depolarization, which results in K⁺ efflux from muscle through K⁺ channel, and elevate K⁺ ion concentration in serum.
• Hypokalemic periodic paralysis (low serum K⁺ ions) is the most common periodic paralysis and has the prevalence of 0.00013%. The mutation in SCN4A and CACNA1S cause an aberrant permeation pathway for H⁺ or Na⁺ and form cation leak currents. The fiber depolarization inactivates Na_v1.4 and Ca_v1.1 channels and induce paralysis.
• Andersen-Tawil syndrome is a rare multiorgan disease characterized by hyperkalemic/hypokalemic periodic paralysis, skeletal malformations, and cardiac arrhythmias (long QT syndrome). KCNJ2 mutations can suppress potassium inward rectifier K_ir2.1 currents and enhance inward currents.

Non-dystrophic myotonias

Non-dystrophic myotonias include myotonia congenita (MC), paramyotonia congenita (PMC) and sodium channel myotonias (SCM).

• Myotonia congenita is a autosomal dominant or autosomal recessive disorder caused by mutations in chloride (ClC-1 coding by CLCN1). The alterations of ClC-1 reduce chloride conductance and hamper muscle relaxation after contraction. Myotonia congenita can be improved by exercise, seen as "warm-up phenomenon".
• Missense mutation in SCN4A gene can cause paramyotonia congenita and sodium channel myotonias. Paramyotonia congenita is an autosomal dominant disorder disease. In contrast to MC, PMC worsens with sustained exercise. It is characterized by early onset muscle stiffness that worsens with cold and exercise, and often accompanied with muscle weakness.
• Sodium channel myotonias are autosomal dominant and characterized by pure myotonia without weakness.