Title: Abnormal intracellular Ca(2+) homeostasis and disease
Authors: Missiaen, Ludwig ×
Robberecht, Wim
Van Den Bosch, Ludo
Callewaert, Geert
Parys, Jan
Wuytack, Frank
Raeymaekers, Luc
Nilius, Bernd
Eggermont, Jan
De Smedt, Humbert #
Issue Date: Jul-2000
Series Title: Cell calcium. vol:28 issue:1 pages:1-21
Abstract: A whole range of cell functions are regulated by the free cytosolic Ca(2+)concentration. Activator Ca(2+)from the extracellular space enters the cell through various types of Ca(2+)channels and sometimes the Na(+)/Ca(2+)-exchanger, and is actively extruded from the cell by Ca(2+)pumps and Na(+)/Ca(2+)-exchangers. Activator Ca(2+)can also be released from internal Ca(2+)stores through inositol trisphosphate or ryanodine receptors and is taken up into these organelles by means of Ca(2+)pumps. The resulting Ca(2+)signal is highly organized in space, frequency and amplitude because the localization and the integrated free cytosolic Ca(2+)concentration over time contain specific information. Mutations or functional abnormalities in the various Ca(2+)transporters, which in vitro seem to induce trivial functional alterations, therefore, often lead to a plethora of diseases. Skeletal-muscle pathology can be caused by mutations in ryanodine receptors (malignant hyperthermia, porcine stress syndrome, central-core disease), dihydropyridine receptors (familial hypokalemic periodic paralysis, malignant hyperthermia, muscular dysgenesis) or Ca(2+)pumps (Brody disease). Ca(2+)-pump mutations in cutaneous epidermal keratinocytes and cochlear hair cells lead to, skin diseases (Darier and Hailey-Hailey) and hearing/vestibular problems respectively. Mutated Ca(2+)channels in the photoreceptor plasma membrane cause vision problems. Hemiplegic migraine, spinocerebellar ataxia type-6, one form of episodic ataxia and some forms of epilepsy can be due to mutations in plasma-membrane Ca(2+)channels, while antibodies against these channels play a pathogenic role in all patients with the Lambert-Eaton myasthenic syndrome and may be of significance in sporadic amyotrophic lateral sclerosis. Brain inositol trisphosphate receptors have been hypothesized to contribute to the pathology in opisthotonos mice, manic-depressive illness and perhaps Alzheimer's disease. Various abnormalities in Ca(2+)-handling proteins have been described in heart during aging, hypertrophy, heart failure and during treatment with immunosuppressive drugs and in diabetes mellitus. In some instances, disease-causing mutations or abnormalities provide us with new insights into the cell biology of the various Ca(2+)transporters.
Description: Afdeling Fysiologie. Afdeling Experimentele neurologie.
ISSN: 0143-4160
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Research Group Experimental Neurology
Laboratory of Molecular and Cellular Signaling
Laboratory of Ion Channel Research
Laboratory for Neurobiology (Vesalius Research Center)
Laboratory of Cellular Transport Systems
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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