Page last updated: 2024-10-24

sarcoplasmic reticulum calcium ion transport

Definition

Target type: biologicalprocess

The directed movement of calcium ions (Ca2+) into, out of or within the sarcoplasmic reticulum. [GOC:BHF, GOC:vk]

Sarcoplasmic reticulum (SR) calcium ion transport is a fundamental process in muscle contraction and relaxation. It involves the movement of calcium ions (Ca2+) across the SR membrane, a specialized intracellular organelle within muscle cells. Here's a detailed breakdown:

1. **Excitation-Contraction Coupling:** The process begins with a nerve impulse arriving at the neuromuscular junction, triggering the release of acetylcholine. Acetylcholine binds to receptors on the muscle fiber membrane, causing depolarization. This depolarization travels along the muscle fiber membrane and into the T-tubules, which are invaginations of the membrane that run deep into the muscle fiber.

2. **Ca2+ Release:** The depolarization of the T-tubules activates voltage-sensitive receptors called dihydropyridine receptors (DHPRs). DHPRs are physically linked to calcium release channels (ryanodine receptors, RyRs) on the SR membrane. Activation of the DHPRs triggers the opening of RyRs, allowing Ca2+ to flood out of the SR into the sarcoplasm, the cytoplasm of the muscle cell.

3. **Muscle Contraction:** The increased concentration of Ca2+ in the sarcoplasm binds to the troponin complex, a protein associated with the thin filament (actin) of the muscle fiber. This binding causes a conformational change in troponin, which moves tropomyosin, another protein associated with actin, away from the myosin-binding sites on actin. Now, the myosin heads, the motor proteins of the thick filament, can bind to actin and initiate the sliding filament mechanism. This results in muscle contraction.

4. **Ca2+ Reuptake:** After the muscle fiber is activated, Ca2+ must be removed from the sarcoplasm to allow relaxation. This is achieved by the SR Ca2+ ATPase (SERCA) pump, an active transporter located in the SR membrane. SERCA uses energy from ATP hydrolysis to pump Ca2+ back into the SR lumen, against its concentration gradient. This process reduces Ca2+ levels in the sarcoplasm, allowing troponin to return to its resting state, and tropomyosin to cover the myosin-binding sites on actin, leading to muscle relaxation.

5. **Regulation of Ca2+ Transport:** The activity of SERCA is regulated by various factors, including:
* **Phosphorylation:** Phosphorylation by protein kinases, such as calcium/calmodulin-dependent protein kinase (CaMK) and protein kinase A (PKA), can activate SERCA, enhancing its Ca2+ pumping capacity.
* **Ca2+ Concentration:** High Ca2+ levels in the sarcoplasm can actually inhibit SERCA, providing a feedback mechanism to fine-tune Ca2+ handling.
* **Other Factors:** Other proteins, like phospholamban (PLN), can also influence SERCA activity, acting as an inhibitor or activator depending on its phosphorylation state.

6. **Role of SR Ca2+ Transport in Muscle Function:** The efficient and regulated transport of Ca2+ by the SR is essential for muscle function. It enables rapid and precise control of muscle contraction and relaxation, allowing for a wide range of muscle activities, from sustained isometric contractions to rapid twitch movements.'
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Proteins (3)

ProteinDefinitionTaxonomy
Ryanodine receptor 2A ryanodine receptor 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92736]Homo sapiens (human)
Voltage-dependent calcium channel gamma-1 subunitA voltage-dependent calcium channel gamma-1 subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q06432]Homo sapiens (human)
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2A sarcoplasmic/endoplasmic reticulum calcium ATPase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P16615]Homo sapiens (human)

Compounds (9)

CompoundDefinitionClassesRoles
tacrinetacrine : A member of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by an amino group at position 9. It is used in the treatment of Alzheimer's disease.

Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.
acridines;
aromatic amine
EC 3.1.1.7 (acetylcholinesterase) inhibitor
2,5-di-tert-butylhydroquinone2,5-di-tert-butylbenzene-1,4-diol : A member of the class of hydroquinones that is benzene-1,4-diol substituted by tert-butyl groups at position 2 and 5.hydroquinones
nimodipinenimodipine : A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a (2-methoxyethoxy)carbonyl group at position 3, a m-nitrophenyl group at position 4, and an isopropoxycarbonyl group at position 5. An L-type calcium channel blocker, it acts particularly on cerebral circulation, and is used both orally and intravenously for the prevention and treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm.

Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
2-methoxyethyl ester;
C-nitro compound;
dicarboxylic acids and O-substituted derivatives;
diester;
dihydropyridine;
isopropyl ester
antihypertensive agent;
calcium channel blocker;
cardiovascular drug;
vasodilator agent
paxillinepaxilline : An indole diterpene alkaloid with formula C27H33NO4 isolated from Penicillium paxilli. It is a potent inhibitor of large conductance Ca2(+)- and voltage-activated K(+) (BK)-type channels.

paxilline: structure given in first source; RN given refers to (2R-(2alpha,4bbeta,6aalpha,12bbeta,12calpha,14abeta))-isomer
diterpene alkaloid;
enone;
organic heterohexacyclic compound;
terpenoid indole alkaloid;
tertiary alcohol
anticonvulsant;
Aspergillus metabolite;
EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitor;
genotoxin;
geroprotector;
mycotoxin;
Penicillium metabolite;
potassium channel blocker
curcumincurcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa.

Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.
aromatic ether;
beta-diketone;
diarylheptanoid;
enone;
polyphenol
anti-inflammatory agent;
antifungal agent;
antineoplastic agent;
biological pigment;
contraceptive drug;
dye;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor;
EC 1.8.1.9 (thioredoxin reductase) inhibitor;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
flavouring agent;
food colouring;
geroprotector;
hepatoprotective agent;
immunomodulator;
iron chelator;
ligand;
lipoxygenase inhibitor;
metabolite;
neuroprotective agent;
nutraceutical;
radical scavenger
ith 4012
chlorantranilipolechlorantranilipole: anthranilic diamide insecticide.that disrupts mating in codling moth (Lepidoptera: Tortricidae)

chlorantraniliprole : A carboxamide resulting from the formal condensation of the carboxylic acid group of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid with the primary amino group of 2-amino-5-chloro-N,3-dimethylbenzamide. The first of the anthranilic diamide insecticides, it is a ryanodine receptor activator and is used to protect a wide variety of crops, including corn, cotton, grapes, rice and potatoes.
monochlorobenzenes;
organobromine compound;
pyrazole insecticide;
pyrazoles;
pyridines;
secondary carboxamide
ryanodine receptor agonist
biselyngbyasidebiselyngbyaside: antineoplastic from the marine cyanobacterium Lyngbya sp.; structure in first source
alpha-cyclopiazonic acidalpha-cyclopiazonic acids