Subcellular properties of [Ca2+]itransients in phospholamban-deficient mouse ventricular cells.
نویسندگان
چکیده
The regulatory protein phospholamban exerts a physiological inhibitory effect on the sarcoplasmic reticulum (SR) Ca2+ pump that is relieved with phosphorylation. We have studied the subcellular properties of intracellular Ca2+([Ca2+]i) transients in ventricular myocytes isolated from wild-type (WT) and phospholamban-deficient (PLB-KO) mice. In PLB-KO myocytes, steady-state twitch [Ca2+]itransients revealed an accelerated relaxation and the occurrence of highly localized failures of Ca2+release. The acceleration of SR Ca2+ uptake caused an increase in SR Ca2+ load with the frequent occurrence of spontaneous [Ca2+]iwaves and Ca2+ sparks. [Ca2+]iwaves in PLB-KO cells showed a marked decrease in spatial width and more frequently appeared to abort. Local Ca2+ release events (Ca2+ sparks) were larger and more variable in amplitude and [Ca2+]ideclined faster in PLB-KO myocytes. Increased local buffering and reduction in the refractoriness of SR Ca2+ release caused by the increased SR pump rate led to an overall enhancement of local [Ca2+]igradients and inhomogeneities in the [Ca2+]idistribution during spontaneous Ca2+ release, [Ca2+]iwaves, and excitation-contraction coupling.
منابع مشابه
Thyroid hormone-induced alterations in phospholamban-deficient mouse hearts.
Alterations in the expression levels of the sarcoplasmic reticulum (SR) Ca2+-ATPase and its regulator, phospholamban, have been implicated in the effects of thyroxine hormone on cardiac function. To determine the role of phospholamban in these effects, hypothyroidism and hyperthyroidism were induced in phospholamban-deficient mice and their isogenic wild types. Hypothyroidism resulted in signif...
متن کاملImmunoelectron microscopical localization of phospholamban in adult canine ventricular muscle
The subcellular distribution of phospholamban in adult canine ventricular myocardial cells was determined by the indirect immunogold-labeling technique. The results presented suggest that phospholamban, like the Ca2+-ATPase, is uniformly distributed in the network sarcoplasmic reticulum but absent from the junctional portion of the junctional sarcoplasmic reticulum. Unlike the Ca2+-ATPase, but ...
متن کاملContractile activity is required for sarcomeric assembly in phenylephrine-induced cardiac myocyte hypertrophy.
Agonist-induced hypertrophy of cultured neonatal rat ventricular myocytes (NRVM) has been attributed to biochemical signals generated during receptor activation. However, NRVM hypertrophy can also be induced by spontaneous or electrically stimulated contractile activity in the absence of exogenous neurohormonal stimuli. Using single-cell imaging of fura 2-loaded myocytes, we found that low-dens...
متن کاملAbnormal myocyte Ca2+homeostasis in rabbits with pacing-induced heart failure.
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 ( I Ca,L) and Na+/Ca2+exchanger current ( I Na/Ca) with voltage clamp and measured intracellular Na+ concentration ([Na+]i) and [Ca2+]iwith the use of sodium-binding benzofuran isop...
متن کاملTargeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation.
Phospholamban is the regulator of the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum (SR), and it has been suggested to be an important determinant in the inotropic responses of the heart to beta-adrenergic stimulation. To determine the role of phospholamban in vivo, the gene coding for this protein was targeted in murine embryonic stem cells, and mice deficient in phospholamban were generated...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- American journal of physiology. Heart and circulatory physiology
دوره 274 5 شماره
صفحات -
تاریخ انتشار 1998