RESUMO
To determine whether there are abnormalities in myocyte excitation-contraction coupling and intracellular Ca2+ concentration ([Ca2+]i) homeostasis in pacing-induced heart failure (PF), we measured L-type Ca2+ current (ICa,L) and Na+/Ca2+ exchanger current (INa/Ca) with voltage clamp and measured intracellular Na+ concentration ([Na+]i) and [Ca2+]i with the use of sodium-binding benzofuran isophthalate (SBFI) and fluo 3 in ventricular myocytes isolated from control and paced rabbits. The peak systolic and diastolic levels and the amplitude of electrically stimulated [Ca2+]i transients (0.25 Hz, extracellular Ca2+ concentration = 1.08 mM) were significantly less in PF myocytes. Also, there was prolongation of the times to peak and decline of [Ca2+]i transients. ICa,L density was markedly decreased in PF myocytes. INa/Ca at -40 mV elicited by rapid exposure to 0 Na+ solution with a rapid solution switcher was significantly reduced in PF myocytes, suggesting that the function of the Na+/Ca2+ exchanger is impaired in these myocytes. In PF myocytes the decline of the [Ca2+]i transient when the Na+/Ca2+ exchanger was abruptly disabled was markedly prolonged compared with the decline in control myocytes, consistent with depressed sarcoplasmic reticulum (SR) Ca2+-ATPase function. RNase protection assay showed decreased levels of Na+/Ca2+ exchanger and SR Ca2+-ATPase mRNA in PF hearts, consistent with the function studies. We conclude that the functions of L-type Ca2+ channels, Na+/Ca2+ exchanger, and SR Ca2+-ATPase are impaired in myocytes from rabbit hearts with failure induced by rapid pacing. These abnormalities result in reduced [Ca2+]i transients and systolic and diastolic dysfunction and appear to account for the abnormal ventricular function observed.
Assuntos
Cálcio/metabolismo , Insuficiência Cardíaca/fisiopatologia , Coração/fisiopatologia , Miocárdio/metabolismo , Marca-Passo Artificial , Animais , Pressão Sanguínea , Peso Corporal , Canais de Cálcio/fisiologia , Canais de Cálcio Tipo L , ATPases Transportadoras de Cálcio/metabolismo , Células Cultivadas , Coração/fisiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Homeostase , Cinética , Tamanho do Órgão , Técnicas de Patch-Clamp , Coelhos , Valores de Referência , Retículo Sarcoplasmático/enzimologia , Sódio/metabolismo , Trocador de Sódio e Cálcio/fisiologiaRESUMO
Progesterone (P), a major hormone of pregnancy, was selected for study under the conditions of an intact utero-placental-fetal unit. A preparation of the canine gravid uterus, near term, is described and shown to permit observation of the metabolic relationships of the steroid hormone P between maternal and fetal organisms. [1,2-3H] P or [7 alpha-3H]P was injected into pups, while [4-14C]P was injected into the uterine circulation. Perfusion was continued for 1 hr with excellent survival of the pups. Identified metabolites in the fetal and maternal tissues suggest a metabolic pool that is shared throughout the unit.