Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of calcium ion transmembrane transport. [GO_REF:0000058, GOC:BHF, GOC:rl, GOC:TermGenie, PMID:24125847]
Negative regulation of calcium ion transmembrane transport is a critical cellular process that controls the movement of calcium ions across cell membranes, playing a crucial role in a wide range of physiological functions, including muscle contraction, neurotransmission, and cell signaling. This process involves a complex interplay of various molecules and mechanisms to regulate the influx and efflux of calcium ions, ensuring that their intracellular levels remain tightly controlled.
Calcium ions are essential for numerous cellular processes, and their concentration within cells must be carefully maintained. Excessive calcium levels can lead to cell damage, while insufficient levels can disrupt normal cellular functions. Therefore, cells have evolved intricate mechanisms to regulate calcium transport, involving both passive and active transport systems.
**Passive Transport:**
* **Diffusion:** Calcium ions can move passively across cell membranes down their concentration gradient, from areas of high concentration to areas of low concentration. This process does not require energy and is influenced by the permeability of the membrane.
**Active Transport:**
* **Calcium pumps (ATPases):** These transmembrane proteins actively transport calcium ions against their concentration gradient, requiring energy derived from ATP hydrolysis. They are responsible for pumping calcium out of the cell or into intracellular storage compartments, such as the endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR).
* **Calcium exchangers:** These transmembrane proteins utilize the electrochemical gradient of another ion (e.g., sodium or potassium) to transport calcium ions. This process is indirect and does not directly require ATP but relies on the existing electrochemical gradients.
**Regulation of Calcium Transport:**
* **Hormonal signaling:** Hormones like parathyroid hormone (PTH) and calcitonin regulate calcium levels in the body by influencing the activity of calcium pumps and channels in bone, kidney, and intestines.
* **Neurotransmitters:** Neurotransmitters like acetylcholine and glutamate can regulate calcium transport in neurons and muscle cells, mediating processes like muscle contraction and synaptic transmission.
* **Calcium-binding proteins:** These proteins, such as calmodulin, bind calcium ions and alter their activity, thereby influencing downstream signaling pathways.
* **Other regulatory mechanisms:** Intracellular signaling pathways, such as the phosphoinositide pathway, can also contribute to the regulation of calcium transport by influencing the activity of calcium pumps, channels, and other proteins involved in calcium homeostasis.
**Negative Regulation:**
* **Inhibition of calcium channels:** Certain proteins can directly block or inhibit the opening of calcium channels, reducing calcium influx into the cell.
* **Activation of calcium pumps:** Stimulation of calcium pumps can lead to increased calcium efflux from the cell, lowering intracellular calcium levels.
* **Downregulation of calcium receptors:** Reducing the number of calcium receptors on the cell surface can decrease the cell's sensitivity to calcium signals.
* **Modulation of calcium-binding proteins:** Changes in the activity or expression of calcium-binding proteins can affect their ability to bind calcium and modulate downstream signaling pathways.
**Consequences of Dysregulation:**
Dysregulation of negative regulation of calcium ion transmembrane transport can contribute to various diseases, including:
* **Muscle weakness and fatigue:** Dysregulation of calcium transport in muscle cells can impair muscle contraction.
* **Neurological disorders:** Disruptions in calcium signaling in neurons can lead to neurological disorders, including epilepsy and Parkinson's disease.
* **Cardiovascular diseases:** Imbalances in calcium homeostasis can contribute to heart rhythm abnormalities and other cardiovascular complications.
**Overall, negative regulation of calcium ion transmembrane transport is a crucial process that ensures appropriate calcium levels within cells, enabling essential physiological functions. Dysregulation of this process can lead to various pathological conditions, highlighting the importance of understanding its complex mechanisms for maintaining health.**'"
| 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) |
| 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 |