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Titolo:
Effects of the protein kinase A inhibitor H-89 on Ca2+ regulation in isolated ferret ventricular myocytes
Autore:
Hussain, M; Drago, GA; Bhogal, M; Colyer, J; Orchard, CH;
Indirizzi:
Univ Leeds, Sch Biomed Sci, Leeds LS2 9NQ, W Yorkshire, England Univ Leeds Leeds W Yorkshire England LS2 9NQ S2 9NQ, W Yorkshire, England Univ Leeds, Sch Biochem & Mol Biol, Leeds LS2 9NQ, W Yorkshire, England Univ Leeds Leeds W Yorkshire England LS2 9NQ S2 9NQ, W Yorkshire, England
Titolo Testata:
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
fascicolo: 4, volume: 437, anno: 1999,
pagine: 529 - 537
SICI:
0031-6768(199903)437:4<529:EOTPKA>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARDIAC SARCOPLASMIC-RETICULUM; CALCIUM-CHANNEL; CALYCULIN-A; 2 SITES; PHOSPHORYLATION; MUSCLE; PHOSPHOLAMBAN; CONTRACTION; MODULATION; MECHANISMS;
Keywords:
calcium; cardiac; cAMP; H-89; protein kinase inhibitors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Hussain, M Univ Leeds, Sch Biomed Sci, Leeds LS2 9NQ, W Yorkshire, EnglandUniv Leeds Leeds W Yorkshire England LS2 9NQ orkshire, England
Citazione:
M. Hussain et al., "Effects of the protein kinase A inhibitor H-89 on Ca2+ regulation in isolated ferret ventricular myocytes", PFLUG ARCH, 437(4), 1999, pp. 529-537

Abstract

We investigated the effects of a protein kinase A (PKA) inhibitor, H-89 {N-[2-(p-bromocinnamylamino)ethyl]-5-iso-quinolinesulphonamide}, on Ca2+ regulation in Fura-2-loaded ferret myocytes. H-89 (10 mu mol/l) decreased the amplitude of the Fura-2 transient to 28.2+/-4.3% (P<0.001) of control and prolonged its duration, characterized by a decrease in the rate of decline ofCa2+ to diastolic levels: t(1/2) increased from 311+/-35 ms to 547+/-43 ms(P<0.001, n=7). Reduced Ca2+ uptake by the sarcoplasmic reticulum (SR) in the presence of H-89 was also indicated by a decrease in the SR Ca2+ content, as assessed with caffeine. The apparent slowing of the SR Ca2+-ATPase was not caused by changes in phosphorylation of phospholamban (PLB). However,Ca2+ uptake in microsomal vesicles prepared from canine hearts and fast-twitch rat skeletal muscle (which lacks PLB) was decreased by 34.1 and 46.8% (n=3), respectively, suggest ing that H-89 has a direct inhibitory effect on the SR Ca2+-ATPase. In electrophysiological experiments, 5.0 mu mol/l H-89 decreased the L-type Ca2+ current (I-Ca) by 39.5% (n=6) and slowed the upstroke of the action potential and, in some cases, caused loss of excitability without changes in the resting membrane potential. In summary, data show that [Ca2+](i) regulation, and hence contraction, is sustained by PKA-mediated phosphorylation, even in the absence of beta-agonists. However, the use of H-89 as a tool to study the role of this signalling pathway is limited by the non-specific effects of H-89 on the SR Ca2+-ATPase.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 19:08:12