Aconitine is a well-known arrhythmogenic toxin and induces triggered activities through cardiac voltage-gated Na(+) channels. However, the effects of aconitine on intracellular Ca(2+) signals were previously unknown. We investigated the effects of aconitine on intracellular Ca(2+) signals in rat ventricular myocytes and explored the possible mechanism of arrhythmogenic toxicity induced by aconi...

BACKGROUND In animal studies, diabetes has been shown to induce changes in gene expression of key regulators in cardiac energy metabolism and calcium homeostasis. In the present study, we tested the hypothesis that metabolic gene expression in nonischemic failing hearts of diabetic patients differs from that in nonischemic failing hearts of nondiabetic patients. METHODS AND RESULTS Left ventr...

AIMS To determine the effects of resistance training (RT) on the expression of microRNA (miRNA)-214 and its target in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), and on the morphological and mechanical properties of isolated left ventricular myocytes. MAIN METHODS Male Wistar rats were divided into two groups (n = 7/group): Control (CO) or trained (TR). The exercise-training protocol consis...

Ca2+-dependent signaling is highly regulated in cardiomyocytes and determines the force of cardiac muscle contraction. Ca2+ cycling refers to the release and reuptake of intracellular Ca2+ that drives muscle contraction and relaxation. In failing hearts, Ca2+ cycling is profoundly altered, resulting in impaired contractility and fatal cardiac arrhythmias. The key defects in Ca2+ cycling occur a...

Sarcolipin, a homologue of phospholamban, regulates Ca2+ uptake through the interaction with sarcoplasmic reticulum Ca2+ ATPase (SERCA) and is predominantly expressed in the atrial muscle. Although the atrial chamber-specific expression of sarcolipin could be primarily regulated at the transcriptional level, the transcriptional regulation remains poorly understood. Since mechanical stress plays...

The sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) is under the control of a closely associated SR protein named phospholamban (PLN). Dephosphorylated PLN inhibits the SR Ca(2+) pump, whereas phosphorylation of PLN, at either Ser(16) by PKA or Thr(17) by calmodulin-dependent protein kinase II (CaMKII), reverses this inhibition, thus increasing SERCA2a activity and the rate of Ca(2+) uptake...

See article by Bluhm et al. [18] (pages 382 –388) in this hypertrophy has led to the proposal that hypertrophy itself issue. may recapitulate ontogeny [13–15]. Therefore, the heart failure process that occurs in the context of myocardial Recent advances in animal genetics and transgenic hypertrophy or complex metabolic disorders that impact technology have blossomed into one of the dominant the...

studying a PLN mutant, PLN, that triggers cardiac failure in humans and mice. Methods and Results—Because PLN inhibits SERCA2a mainly by preventing deactivation of wild-type PLN, SERCA2a activity could be increased stepwise by generating mice that carry a PLN transgene and 2, 1, or 0 endogenous PLN alleles (PLN / TgPLN, PLN / TgPLN, and PLN / TgPLN, respectively). PLN / TgPLN hearts demonstrate...