Abstract
Transient elevations of intracellular Ca$^2+$ play a signalling
role in such complex cellular functions as contraction, secretion,
fertilization, proliferation, metabolism, heartbeat and memory. However,
prolonged elevation of Ca$^2+$ above about 10 microM is deleterious
to a cell and can activate apoptosis. In muscle, there is a narrow
window of Ca$^2+$ dysregulation in which abnormalities in Ca$^2+$
regulatory proteins can lead to disease, rather than apoptosis. Key
proteins in the regulation of muscle Ca$^2+$ are the voltage-dependent,
dihydropyridine-sensitive, L-type Ca$^2+$ channels located in
the transverse tubule and Ca$^2+$ release channels in the junctional
terminal cisternae of the sarcoplasmic reticulum. Abnormalities in
these proteins play a key role in malignant hyperthermia (MH), a
toxic response to anesthetics, and in central core disease (CCD),
a muscle myopathy. Sarco(endo)plasmic reticulum Ca$^2+$ ATPases
(SERCAs) return sarcoplasmic Ca$^2+$ to the lumen of the sarcoplasmic
reticulum. Loss of SERCA1a Ca$^2+$ pump function is one cause
of exercise-induced impairment of the relaxation of skeletal muscle,
in Brody disease. Phospholamban expressed in cardiac muscle and sarcolipin
expressed in skeletal muscle regulate SERCA activity. Studies with
knockout and transgenic mice show that gain of inhibitory function
of phospholamban alters cardiac contractility and could be a causal
feature in some cardiomyopathies. Calsequestrin, calreticulin, and
a series of other acidic, lumenal, Ca$^2+$ binding proteins provide
a buffer for Ca$^2+$ stored in the sarcoplasmic reticulum. Overexpression
of cardiac calsequestrin leads to cardiomyopathy and ablation of
calreticulin alters cardiac development.
- 10951187
- animals,
- calcium
- calcium-bindi,
- calreticulin,
- calsequestrin,
- central
- channels,
- core,
- gov't,
- humans,
- hyperthermia,
- knockout,
- l-type,
- malignant
- mice,
- mutation,
- myopathy,
- ng
- non-u.s.
- proteins,
- research
- ribonucleoproteins,
- signaling,
- support,
- transgenic,
Users
Please
log in to take part in the discussion (add own reviews or comments).