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regulation of cardiac muscle cell membrane potential

Definition

Target type: biologicalprocess

Any process that modulates the establishment or extent of a membrane potential in a cardiac muscle cell (a cardiomyocyte). A membrane potential is the electric potential existing across any membrane arising from charges in the membrane itself and from the charges present in the media on either side of the membrane. [GOC:BHF, GOC:mtg_cardiac_conduct_nov11]

The regulation of cardiac muscle cell membrane potential is a complex process that involves the coordinated activity of various ion channels and transporters. The resting membrane potential of a cardiac muscle cell is typically around -90 mV, which is maintained by the sodium-potassium pump, a transmembrane protein that actively transports sodium ions out of the cell and potassium ions into the cell. This creates a concentration gradient that favors the movement of potassium ions out of the cell and sodium ions into the cell.

The opening of voltage-gated sodium channels during the depolarization phase of an action potential allows sodium ions to flow into the cell, rapidly depolarizing the membrane potential. This depolarization wave then spreads throughout the cell, triggering the opening of voltage-gated calcium channels. These channels are responsible for the plateau phase of the cardiac action potential, which is characterized by a sustained depolarization. The prolonged duration of the plateau phase is essential for the contraction of cardiac muscle cells.

The influx of calcium ions through the voltage-gated calcium channels also activates the ryanodine receptors, which are calcium channels located on the sarcoplasmic reticulum. The opening of these channels releases a large amount of calcium ions into the cytoplasm, further increasing the intracellular calcium concentration. This rise in intracellular calcium concentration triggers the contraction of the cardiac muscle cell.

As the action potential progresses, the voltage-gated sodium channels inactivate and the potassium channels open. The efflux of potassium ions out of the cell repolarizes the membrane potential, returning it to its resting state.

The regulation of cardiac muscle cell membrane potential is also influenced by the activity of other ion channels and transporters, such as the sodium-calcium exchanger and the potassium-chloride cotransporter. The sodium-calcium exchanger removes calcium ions from the cell by exchanging them for sodium ions. The potassium-chloride cotransporter regulates the intracellular chloride concentration, which can influence the membrane potential.

The regulation of cardiac muscle cell membrane potential is essential for normal heart function. Any disruption in the function of the ion channels or transporters involved in this process can lead to cardiac arrhythmias, which can be life-threatening. Therefore, understanding the mechanisms underlying the regulation of cardiac muscle cell membrane potential is crucial for the diagnosis and treatment of heart disease.'
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Proteins (3)

ProteinDefinitionTaxonomy
Mitochondrial sodium/calcium exchanger proteinA mitochondrial sodium/calcium exchanger protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6J4K2]Homo sapiens (human)
Sodium/hydrogen exchanger 1A sodium/hydrogen exchanger 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P19634]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 (15)

CompoundDefinitionClassesRoles
ethylisopropylamilorideethylisopropylamiloride : A member of the class of pyrazines that is amiloride in which the amino substitutent of the pyrazine ring that is adjacent to the chloro substituent has been substituted by an ethyl group and by an isopropyl group.

ethylisopropylamiloride: structure in first source
aromatic amine;
guanidines;
monocarboxylic acid amide;
organochlorine compound;
pyrazines;
tertiary amino compound
anti-arrhythmia drug;
neuroprotective agent;
sodium channel blocker
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
cgp 37157CGP 37157: benzothiazepine derivative of clonazepam; inhibits the in vitro activity of mitochondrial sodium-calcium exchangebenzothiazepine
benzotriazolebenzotriazole : The simplest member of the class of benzotriazoles that consists of a benzene nucleus fused to a 1H-1,2,3-triazole ring.

benzotriazole: inhibitor of atmospheric metal corrosion; also component of motion picture film & Neva brake fluid
benzotriazolesenvironmental contaminant;
xenobiotic
amilorideamiloride : A member of the class of pyrazines resulting from the formal monoacylation of guanidine with the carboxy group of 3,5-diamino-6-chloropyrazine-2-carboxylic acid.

Amiloride: A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
aromatic amine;
guanidines;
organochlorine compound;
pyrazines
diuretic;
sodium channel blocker
amiloride hydrochlorideamiloride hydrochloride dihydrate : A hydrate that is the dihydrate of amiloride hydrochloride.hydratediuretic;
sodium channel blocker
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
cariporidecariporide: a selective sodium-hydrogen exchange subtype 1 inhibitor; structure in first source
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
eniporideeniporide: inhibits NHE-1 isoform; structure in first source
zoniporidezoniporide: inhibits sodium-hydrogen exchanger isoform-1 (NHE-1)
sabiporidesabiporide: a NHE-1 inhibitor and a cardioprotective agent; structure in first source
(5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl)guanidine(5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl)guanidine: KR-32570 possesses potent cardioprotective effects in perfused rat hearts, and its effects may be mediated by inhibition of NHE-1, preservation of high-energy phosphates, and inhibition of lipid peroxidation
biselyngbyasidebiselyngbyaside: antineoplastic from the marine cyanobacterium Lyngbya sp.; structure in first source
alpha-cyclopiazonic acidalpha-cyclopiazonic acids