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Original paragraph[edit]

A calciumopathy is a disease caused by disruption to the use of calcium within a cell. To a large extent, a calciumopathy is a type of channelopathy, or a disease caused by disturbed function of ion channel subunits or the proteins that regulate them; calciumopathies also include dysfunctions of regulatory pathways and mitochondria. Many calciumopathies are complex polygenic diseases; clues to their understanding are coming from the rarer monogenic forms of common symptoms such as seizures, ataxia, and migraine.

Calciumopathy[edit]

Calciumopathies are calcium signaling diseases. They are caused by disruptions of intracellular calcium homeostasis.[1]The calcium ion is one of the most versatile, ancient, and universal of biological signaling molecules, known to regulate physiological systems at every level from membrane potential and ion transporters to kinases and transcription factors.[1] A major feature of calciumopathies in excitable tissue is a periodic disruption of rhythmic activity which results in a specific functional impairment.[2]

Human genetic diseases caused by calcium channel gene mutation[edit]

Calcium channels consist of calcium entry channels and calcium release channels. Calcium entry channels let Ca+ enter cells from extracellular space. Calcium entry channel includes voltage-gated calcium (VGC) channel regulated by membrane depolarization and ligand-gated calcium channel (LGC) regulated by chemical information, such as glutamate. Calcium release channels let calcium released from the storing Ca+ signal organelles to cytosome. Ryanodine receptor (RYR) and inositol-1,4,5-triphosphosate (IP3) are examples of calcium release channels which go through this pathway.[3] VGC mutations and RYR mutations in calcium channels have been found related to human genetic disease. Different subunit mutation in VGC gene may lead to familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6), hypokalemic periodic paralysis (HPP), congenital stationary night blindness (CSNB) and epilepsy.[4] RYR1 mutation may lead malignant hyperthermia (MH) and central core disease (CCD).[5][6]Alzheimer's disease (AD) is considered to relate to calciumopathy critically.[7]

Calciumopathies in Nervous system[edit]

According to Lorenzon (2000) "Neuronal calcium channels have many cellular functions including: control of neurotransmitter release, regulation of gene expression, integration and propagation of postsynaptic signals, and neurite outgrowth.[3] To change the signaling pathways, calcium channel mutations would probably cause cytotoxicity. Both increased and decreased intracellular Ca2+ have been reported to be cytotoxic to neurons."

Mutations in different subunit in nervous system cause different diseases. Mutations of α1F subunit cause Incomplete X-linked congenital stationary night blindness (incomplete xlCSNB). Mutations in the a1A calcium channel subunit will cause the human autosomal-dominant neurological disorders of familial hemiplegic migraine (FHM), episodic ataxia type-2, spinocerebellar ataxia-6, episodic-and-progressive ataxia, Tottering, and Leaner. Mutations in auxiliary subunits of calcium channels have been shown to produce Lethargic and Stargazer.[3]

Calciumopathies of Muscle[edit]

Calcium channel defects have been proved to involve several human muscle diseases: hypokalemic periodic paralysis (HypoPP), malignant hyperthermia (MH) and central core disease (CCD). The mutations that have caused these diseases have been located in the region of calcium channels related to excitation-contraction (E-C) coupling. [3]

Heart attack[edit]

Calcium signaling lies at the heart of almost everything we do.[2] The disruption of rhythmic activity in cardiac muscles produces a fatal arrhythmia, owing to delayed repolarization of the cardiac myocytes followed a heartbeat. A condition of delayed repolarization is known as long QT syndrom. Hereditary calciumopathies include Long QT syndrome, Catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada syndrome (BrS), and Short QT syndrome. Non-hereditary calciumopathies include cardiomyopathy, heart failure (HF), and Atrial fibrillation (AF or A-fib).

Calcium channels related heart attack attract extensive attention. Because it has high incidence of sudden cardiac death and severe clinical manifestations. Calcium channel arrhythmia treatment is mainly dependent on calcium channel blockers (CCB) and β-blockers. CCB is also used to treat hypertension.

  1. ^ a b Gargus, J. Jay (2009-01-01). "Genetic Calcium Signaling Abnormalities in the Central Nervous System: Seizures, Migraine, and Autism". Annals of the New York Academy of Sciences. 1151 (1): 133–156. doi:10.1111/j.1749-6632.2008.03572.x. ISSN 1749-6632.
  2. ^ a b Chakroborty, Shreaya; Stutzmann, Grace E. (2014-09-15). "Calcium channelopathies and Alzheimer's disease: insight into therapeutic success and failures". European Journal of Pharmacology. 739: 83–95. doi:10.1016/j.ejphar.2013.11.012. ISSN 1879-0712. PMID 24316360.
  3. ^ a b c d Lorenzon, Nancy M.; Beam, Kurt G. (2000-03-01). "Calcium channelopathies". Kidney International. 57 (3): 794–802. doi:10.1046/j.1523-1755.2000.00917.x. ISSN 0085-2538.
  4. ^ "钙离子通道与人类遗传病 - 中华儿科杂志". zhekzz.yiigle.com. Retrieved 2015-11-12.
  5. ^ Loke, J.; MacLennan, D. H. (1998-05-01). "Malignant hyperthermia and central core disease: disorders of Ca2+ release channels". The American Journal of Medicine. 104 (5): 470–486. ISSN 0002-9343. PMID 9626031.
  6. ^ Robinson, Rachel L.; Brooks, Collin; Brown, Sarah L.; Ellis, F. Richard; Halsall, P. Jane; Quinnell, Rupert J.; Shaw, Marie-Anne; Hopkins, Philip M. (2002-08-01). "RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes". Human Mutation. 20 (2): 88–97. doi:10.1002/humu.10098. ISSN 1098-1004. PMID 12124989.
  7. ^ Chakroborty, Shreaya; Stutzmann, Grace E. (2011-08-01). "Early calcium dysregulation in Alzheimer's disease: setting the stage for synaptic dysfunction". Science China. Life Sciences. 54 (8): 752–762. doi:10.1007/s11427-011-4205-7. ISSN 1869-1889. PMID 21786198.
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