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001-es BibID:BIBFORM009063
Első szerző:Alvarez, Julio
Cím:ATP/UTP activate cation-permeable channels with TRPC3/7 properties in rat cardiomyocytes / Alvarez, J., Coulombe, A., Cazorla, O., Ugur, M., Rauzier, J. M., Magyar, J., Mathieu, E. L., Boulay, G., Souto, R., Bideaux, P., Salazar, G., Rassendren, F., Lacampagne, A., Fauconnier, J., Vassort, G.
ISSN:0363-6135 (Print)
Megjegyzések:Extracellular purines and pyrimidines have major effects on cardiac rhythm and contraction. ATP/UTP are released during various physiopathological conditions, such as ischemia, and despite degradation by ectonucleotidases, their interstitial concentrations can markedly increase, a fact that is clearly associated with arrhythmia. In the present whole cell patch-clamp analysis on ventricular cardiomyocytes isolated from various mammalian species, ATP and UTP elicited a sustained, nonselective cationic current, I(ATP). UDP was ineffective, whereas 2'(3')-O-(4-benzoylbenzoyl)-ATP was active, suggesting that P2Y(2) receptors are involved. I(ATP) resulted from the binding of ATP(4-) to P2Y(2) purinoceptors. I(ATP) was maintained after ATP removal in the presence of guanosine 5'-[gamma-thio]triphosphate and was inhibited by U-73122, a PLC inhibitor. Single-channel openings are rather infrequent under basal conditions. ATP markedly increased opening probability, an effect prevented by U-73122. Two main conductance levels of 14 and 23 pS were easily distinguished. Similarly, in fura-2-loaded cardiomyocytes, Mn(2+) quenching and Ba(2+) influx were significant only in the presence of ATP or UTP. Adult rat ventricular cardiomyocytes expressed transient receptor potential channel TRPC1, -3, -4, and -7 mRNA and the TRPC3 and TRPC7 proteins that coimmunoprecipitated. Finally, the anti-TRPC3 antibody added to the patch pipette solution inhibited I(ATP). In conclusion, activation of P2Y(2) receptors, via a G protein and stimulation of PLCbeta, induces the opening of heteromeric TRPC3/7 channels, leading to a sustained, nonspecific cationic current. Such a depolarizing current could induce cell automaticity and trigger the arrhythmic events during an early infarct when ATP/UTP release occurs. These results emphasize a new, potentially deleterious role of TRPC channel activation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adenosine Triphosphate
Arrhythmias, Cardiac
Cell Membrane Permeability
Disease Models, Animal
Membrane Potentials
Mice, Knockout
Myocardial Infarction
Myocytes, Cardiac
Patch-Clamp Techniques
Phosphodiesterase Inhibitors
Phospholipase C beta
Rats, Wistar
Receptors, Purinergic P2
Signal Transduction
TRPC Cation Channels
Uridine Triphosphate
Megjelenés:American Journal of Physiology. Heart and Circulatory Physiology. - 295 (2008), p. H21-H28. -
További szerzők:Coulombe, Alaine Cazorla, Olivier Ugur, Mehmet Rauzier, Jean-Michel Magyar János (1961-) (élettanász) Mathieu, Eve-Lyne Boulay, Guylain Souto, Rafael Bideaux, Patrice Salazar, Guillermo Rassendren, Francois Lacampagne, Alain Fauconnier, Jérémy Vassort, Guy
Internet cím:DOI
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