negative regulation of calcium:sodium antiporter activity
Definition
Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of calcium:sodium antiporter activity. [GO_REF:0000059, GOC:BHF, GOC:mtg_cardiac_conduct_nov11, GOC:rl, GOC:TermGenie, PMID:19683723]
Negative regulation of calcium:sodium antiporter activity refers to the cellular processes that decrease the activity of calcium:sodium exchangers, transmembrane proteins responsible for transporting calcium ions (Ca2+) out of the cell and sodium ions (Na+) into the cell. This regulation is crucial for maintaining calcium homeostasis, a vital aspect of cellular signaling, muscle contraction, and neuronal function.
Several mechanisms contribute to the negative regulation of calcium:sodium antiporter activity, including:
1. **Phosphorylation:** Kinases, such as protein kinase C (PKC), can phosphorylate specific residues on the calcium:sodium antiporter, leading to a conformational change that reduces its activity.
2. **Calcium-dependent inactivation:** High intracellular calcium levels can directly inhibit the antiporter's activity, acting as a feedback mechanism to prevent excessive calcium efflux.
3. **Protein-protein interactions:** Interactions with other proteins, such as calmodulin or specific regulatory subunits, can modulate the antiporter's function.
4. **Membrane trafficking:** The antiporter can be sequestered away from the plasma membrane through endocytosis, reducing its availability for calcium transport.
5. **Transcriptional regulation:** The expression of genes encoding calcium:sodium antiporters can be downregulated, leading to a decrease in the overall number of antiporters present in the cell.
These regulatory mechanisms ensure that calcium levels are tightly controlled, preventing potentially harmful fluctuations that could disrupt cellular function. The precise mechanisms and their relative importance vary depending on the cell type and the specific context. For instance, in neurons, the regulation of calcium:sodium antiporters is crucial for maintaining neuronal excitability and synaptic transmission.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Sodium/potassium-transporting ATPase subunit alpha-2 | A sodium/potassium-transporting ATPase subunit alpha-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P50993] | Homo sapiens (human) |
Compounds (14)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| lansoprazole | Lansoprazole: A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers. | benzimidazoles; pyridines; sulfoxide | anti-ulcer drug; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor |
| omeprazole | 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole : A member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a [4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl group at position 2 and a methoxy group at position 5. omeprazole : A racemate comprising equimolar amounts of (R)- and (S)-omeprazole. Omeprazole: A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. | aromatic ether; benzimidazoles; pyridines; sulfoxide | |
| pantoprazole | pantoprazole : A member of the class of benzimidazoles that is 1H-benzimidazole substituted by a difluoromethoxy group at position 5 and a [(3,4-dimethoxypyridin-2-yl)methyl]sulfinyl group at position 2. Pantoprazole: 2-pyridinylmethylsulfinylbenzimidazole proton pump inhibitor that is used in the treatment of GASTROESOPHAGEAL REFLUX and PEPTIC ULCER. | aromatic ether; benzimidazoles; organofluorine compound; pyridines; sulfoxide | anti-ulcer drug; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor; environmental contaminant; xenobiotic |
| digoxigenin | digoxigenin : A hydroxy steroid that consists of 5beta-cardanolide having a double bond at the 20(22)-position as well as hydroxy groups at the 3beta-, 12beta- and 14beta-positions. It has been isolated from the plant species of the genus Digitalis. Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. | 12beta-hydroxy steroid; 14beta-hydroxy steroid; 3beta-hydroxy steroid; 3beta-sterol | hapten; plant metabolite |
| digoxigenin-bis(digitoxoside) | cardenolide glycoside | ||
| rostafuroxin | rostafuroxin: structure in first source | ||
| ouabain | cardiac glycoside : Steroid lactones containing sugar residues that act on the contractile force of the cardiac muscles. ouabain : A steroid hormone that is a multi-hydroxylated alpha-L-rhamnosyl cardenoloide. It binds to and inhibits the plasma membrane Na(+)/K(+)-ATPase (sodium pump). It has been isolated naturally from Strophanthus gratus. Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE. | 11alpha-hydroxy steroid; 14beta-hydroxy steroid; 5beta-hydroxy steroid; alpha-L-rhamnoside; cardenolide glycoside; steroid hormone | anti-arrhythmia drug; cardiotonic drug; EC 2.3.3.1 [citrate (Si)-synthase] inhibitor; EC 3.1.3.41 (4-nitrophenylphosphatase) inhibitor; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor; EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor; ion transport inhibitor; plant metabolite |
| digitoxin | digitoxin : A cardenolide glycoside in which the 3beta-hydroxy group of digitoxigenin carries a 2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl trisaccharide chain. Digitoxin: A cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting. (From Martindale, The Extra Pharmacopoeia, 30th ed, p665) | cardenolide glycoside | EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor |
| digoxin | digoxin : A cardenolide glycoside that is digitoxin beta-hydroxylated at C-12. A cardiac glycoside extracted from the foxglove plant, Digitalis lanata, it is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation, but the margin between toxic and therapeutic doses is small. Digoxin: A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) | cardenolide glycoside; steroid saponin | anti-arrhythmia drug; cardiotonic drug; EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor; epitope |
| digitoxigenin | digitoxigenin : A 5beta-cardenolide that is 5beta-cardanolide with hydroxy substituents at the 3beta- and 14beta-positions and double bond unsaturation at C(20)-C(22). Digitoxigenin: 3 beta,14-Dihydroxy-5 beta-card-20(22)enolide. A cardenolide which is the aglycon of digitoxin. Synonyms: Cerberigenin; Echujetin; Evonogenin; Thevetigenin. | 14beta-hydroxy steroid; 3beta-hydroxy steroid | |
| phakellistatin 2 | phakellistatin 2: isolated from the marine sponge Phakellia carteri; structure in first source | ||
| digitoxigenin monodigitoxoside | digitoxigenin monodigitoxoside: RN given refers to (ribo-3beta,5beta)-isomer | ||
| evomonoside | evomonoside : A cardenolide glycoside consisting of digitoxigenin having an alpha-L-rhamnosyl moiety attached at the O(3)-position. evomonoside: a cytotoxic cardiac glycoside from Lepidium apetalum; RN refers to (3beta,5beta)-isomer | cardenolide glycoside | |
| halisulfate 1 | halisulfate 1: an isocitrate lyase inhibitor sesterterpene sulfate from sponge, Hippospongia sp.; structure in first source | organic molecular entity | metabolite |