Target type: biologicalprocess
The process in which ions are transported across the plasma membrane of a ventricular cardiac muscle cell such that the membrane potential changes in the repolarizing direction, toward the steady state potential. For example, the repolarization during an action potential is from a positive membrane potential towards a negative resting potential. [GOC:BHF, GOC:mtg_cardiac_conduct_nov11]
Ventricular cardiac muscle cell membrane repolarization is a crucial process that restores the resting membrane potential of these cells after an action potential, enabling them to contract again. Here's a detailed breakdown:
1. **Sodium Channel Inactivation:** As the depolarization phase of the action potential peaks, sodium channels rapidly inactivate, preventing further influx of sodium ions. This marks the beginning of repolarization.
2. **Potassium Channel Activation:** Simultaneously, the rising intracellular calcium concentration during depolarization triggers the opening of voltage-gated potassium channels (Kv channels). These channels allow potassium ions to flow out of the cell, driven by their concentration gradient.
3. **Rapid Repolarization:** The efflux of potassium ions rapidly repolarizes the membrane potential, bringing it back towards its resting value. This phase is characterized by a steep downward slope on the action potential waveform.
4. **Plateau Phase:** In ventricular myocytes, there's a brief plateau phase after the rapid repolarization. This is due to the activation of L-type calcium channels, which allow calcium ions to enter the cell, partially counteracting the potassium efflux. The plateau phase contributes to the prolonged action potential duration in ventricular cells, crucial for synchronized contraction.
5. **Delayed Repolarization:** Following the plateau phase, the L-type calcium channels close, and the potassium efflux continues through Kv channels, gradually restoring the resting membrane potential. This phase is slower than the initial repolarization.
6. **Resting Membrane Potential:** Repolarization concludes with the membrane potential returning to its resting value, typically around -90 mV. This state allows the cell to be ready for another action potential, enabling continued heart rhythm and function.
7. **Ion Pumps:** The sodium-potassium pump actively transports sodium ions out of the cell and potassium ions back in, maintaining the concentration gradients essential for repolarization. This process ensures that the cell is ready for the next action potential cycle.
8. **Role of Calcium:** The influx of calcium during the plateau phase not only contributes to the action potential duration but also initiates the intracellular cascade that leads to muscle contraction.
9. **Importance of Repolarization:** Proper repolarization is vital for the heart's electrical activity. Disruptions in repolarization can lead to arrhythmias (irregular heartbeats) and potentially life-threatening conditions.
In summary, ventricular cardiac muscle cell membrane repolarization is a tightly regulated process involving the interplay of ion channels, membrane permeability, and ion pumps. It ensures that the heart can efficiently contract and relax, sustaining a regular and effective heartbeat.'
"
| Protein | Definition | Taxonomy |
|---|---|---|
| Potassium voltage-gated channel subfamily D member 3 | A voltage-gated potassium channel KCND3 that is encoded in the genome of human. [PRO:CNA, UniProtKB:Q9UK17] | Homo sapiens (human) |
| G protein-activated inward rectifier potassium channel 1 | A G protein-activated inward rectifier potassium channel 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P48549] | Homo sapiens (human) |
| G protein-activated inward rectifier potassium channel 4 | A G protein-activated inward rectifier potassium channel 4 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P48544] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| N-(2-aminoethyl)-5-chloro-1-naphthalenesulfonamide | naphthalenes; sulfonic acid derivative | ||
| alfuzosin | alfuzosin: structure given in first source | monocarboxylic acid amide; quinazolines; tetrahydrofuranol | alpha-adrenergic antagonist; antihypertensive agent; antineoplastic agent |
| duloxetine | duloxetine | ||
| nelfinavir | nelfinavir : An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties. Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. | aryl sulfide; benzamides; organic heterobicyclic compound; phenols; secondary alcohol; tertiary amino compound | antineoplastic agent; HIV protease inhibitor |
| nebivolol | 2,2'-iminobis[1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol] : A member of the class of chromanes that is 2,2'-iminodiethanol in which one hydrogen attached to each hydroxy-bearing carbon is replaced by a 6-fluorochroman-2-yl group. | chromanes; diol; organofluorine compound; secondary alcohol; secondary amino compound | |
| paliperidone | 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one : A member of the class of pyridopyrimidines that is 9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one carrying an additional 2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl group at position 2. paliperidone : A racemate comprising equimolar amounts of (R)- and (S)-paliperidone. Paliperidone is the primary active metabolite of the older antipsychotic risperidone and is used for treatment of schizophrenia. | 1,2-benzoxazoles; heteroarylpiperidine; organofluorine compound; pyridopyrimidine; secondary alcohol | |
| desvenlafaxine | O-desmethylvenlafaxine : A tertiary amino compound that is N,N-dimethylethanamine substituted at position 1 by a 1-hydroxycyclohexyl and 4-hydroxyphenyl group. It is a metabolite of the drug venlafaxine. | cyclohexanols; phenols; tertiary amino compound | antidepressant; drug metabolite; marine xenobiotic metabolite |
| solifenacin | isoquinolines | ||
| etravirine | aminopyrimidine; aromatic ether; dinitrile; organobromine compound | antiviral agent; HIV-1 reverse transcriptase inhibitor | |
| darunavir | darunavir : An N,N-disubstituted benzenesulfonamide bearing an unsubstituted amino group at the 4-position, used for the treatment of HIV infection. A second-generation HIV protease inhibitor, darunavir was designed to form robust interactions with the protease enzyme from many strains of HIV, including those from treatment-experienced patients with multiple resistance mutations to other protease inhibitors. Darunavir: An HIV PROTEASE INHIBITOR that is used in the treatment of AIDS and HIV INFECTIONS. Due to the emergence of ANTIVIRAL DRUG RESISTANCE when used alone, it is administered in combination with other ANTI-HIV AGENTS. | carbamate ester; furofuran; sulfonamide | antiviral drug; HIV protease inhibitor |
| deferasirox | deferasirox : A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions. Deferasirox: A triazole and benzoate derivative that acts as a selective iron chelator. It is used in the management of chronic IRON OVERLOAD due to blood transfusion or non-transfusion dependent THALASSEMIA. | benzoic acids; monocarboxylic acid; phenols; triazoles | iron chelator |
| naringin | (2S)-flavan-4-one; 4'-hydroxyflavanones; dihydroxyflavanone; disaccharide derivative; neohesperidoside | anti-inflammatory agent; antineoplastic agent; metabolite | |
| tolterodine | tertiary amine | antispasmodic drug; muscarinic antagonist; muscle relaxant | |
| darifenacin | darifenacin : 2-[(3S)-1-Ethylpyrrolidin-3-yl]-2,2-diphenylacetamide in which one of the hydrogens at the 2-position of the ethyl group is substituted by a 2,3-dihydro-1-benzofuran-5-yl group. It is a selective antagonist for the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions, and is used as the hydrobromide salt in the management of urinary incontinence. | 1-benzofurans; monocarboxylic acid amide; pyrrolidines | antispasmodic drug; muscarinic antagonist |
| s 1033 | (trifluoromethyl)benzenes; imidazoles; pyridines; pyrimidines; secondary amino compound; secondary carboxamide | anticoronaviral agent; antineoplastic agent; tyrosine kinase inhibitor | |
| 1-[5-(ethylthio)-1,3,4-thiadiazol-2-yl]-3-[1,1,1-trifluoro-2-(trifluoromethyl)butan-2-yl]urea | thiadiazoles; ureas | ||
| 1-(3-chlorophenyl)-3-(2-phenoxyphenyl)thiourea | aromatic ether | ||
| 3-bromo-4-methoxy-N-[(propan-2-ylamino)-sulfanylidenemethyl]benzamide | carbonyl compound; organohalogen compound | ||
| dasatinib | dasatinib (anhydrous) : An aminopyrimidine that is 2-methylpyrimidine which is substituted at position 4 by the primary amino group of 2-amino-1,3-thiazole-5-carboxylic acid and at position 6 by a 4-(2-hydroxyethyl)piperazin-1-yl group, and in which the carboxylic acid group has been formally condensed with 2-chloro-6-methylaniline to afford the corresponding amide. A multi-targeted kinase inhibitor, it is used, particularly as the monohydrate, for the treatment of chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia. Note that the name 'dasatinib' is used to refer to the monohydrate (USAN) as well as to anhydrous dasatinib (INN). N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1,3-thiazole-5-carboxamide: a dasatinib prodrug; structure in first source | 1,3-thiazoles; aminopyrimidine; monocarboxylic acid amide; N-(2-hydroxyethyl)piperazine; N-arylpiperazine; organochlorine compound; secondary amino compound; tertiary amino compound | anticoronaviral agent; antineoplastic agent; tyrosine kinase inhibitor |
| 1-(4-butylphenyl)-3-[4-chloro-3-(dimethylsulfamoyl)phenyl]thiourea | sulfonamide | ||
| 1-(4-chlorophenyl)-3-[2-(2-furanylmethyl)cyclohexyl]urea | ureas | ||
| sitagliptin | sitagliptin : A triazolopyrazine that exhibits hypoglycemic activity. | triazolopyrazine; trifluorobenzene | EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor; environmental contaminant; hypoglycemic agent; serine proteinase inhibitor; xenobiotic |
| acacetin | 5,7-dihydroxy-4'-methoxyflavone : A monomethoxyflavone that is the 4'-methyl ether derivative of apigenin. | dihydroxyflavone; monomethoxyflavone | anticonvulsant; plant metabolite |
| silodosin | silodosin: an alpha(1a)-adrenoceptor-selective antagonist; structure given in first source | indolecarboxamide | |
| su 11248 | monocarboxylic acid amide; pyrroles | angiogenesis inhibitor; antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; immunomodulator; neuroprotective agent; vascular endothelial growth factor receptor antagonist | |
| everolimus | cyclic acetal; cyclic ketone; ether; macrolide lactam; primary alcohol; secondary alcohol | anticoronaviral agent; antineoplastic agent; geroprotector; immunosuppressive agent; mTOR inhibitor | |
| 6-cyano-4-(n-ethylsulfonyl-n-methylamino)-3-hydroxy-2,2-dimethylchromane, (trans-(+))-isomer | |||
| lu 208075 | ambrisentan: an ET(A) receptor antagonist and antihypertensive agent; studied for use in pulmonary arterial hypertension | diarylmethane | |
| raltegravir | 1,2,4-oxadiazole; dicarboxylic acid amide; hydroxypyrimidine; monofluorobenzenes; pyrimidone; secondary carboxamide | antiviral drug; HIV-1 integrase inhibitor | |
| sildenafil | sildenafil : A pyrazolo[4,3-d]pyrimidin-7-one having a methyl substituent at the 1-position, a propyl substituent at the 3-position and a 2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl group at the 5-position. | piperazines; pyrazolopyrimidine; sulfonamide | EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor; vasodilator agent |
| vardenafil | vardenafil : The sulfonamide resulting from formal condensation of the sulfo group of 4-ethoxy-3-(5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(1H)-one-2-yl)benzenesulfonic acid and the secondary amino group of 4-ethylpiperazine. | imidazotriazine; N-alkylpiperazine; N-sulfonylpiperazine | EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; vasodilator agent |
| amg531 |