Pieter P . de Tombe

Learn More
Blebbistatin (BLEB) is a recently discovered compound that inhibits myosin-II ATPase activity. In this study, we tested BLEB in intact and skinned isolated rat cardiac trabeculae, rat intact myocytes, and single rabbit psoas myofibrils. BLEB (10 μM) reduced twitch force and cell shortening that was reversed by exposure to light. BLEB treatment of skinned(More)
The present study examined the contribution of myofilament contractile proteins to regional function in guinea pig myocardium. We investigated the effect of stretch on myofilament contractile proteins, Ca2+ sensitivity, and cross-bridge cycling kinetics (K tr) of force in single skinned cardiomyocytes isolated from the sub-endocardial (ENDO) or(More)
This study was conducted to identify molecular mechanisms which explain interventricular differences in myofilament function in experimental congestive heart failure (CHF). CHF was induced in rats by chronic aortic banding or myocardial infarction for 32–36 weeks. Right and left ventricular (RV, LV) myocytes were mechanically isolated, triton-skinned, and(More)
Myocardial contraction is initiated upon the release of calcium into the cytosol from the sarcoplasmic reticulum following membrane depolarization. The fundamental physiological role of the heart is to pump an amount blood that is determined by the prevailing requirements of the body. The physiological control systems employed to accomplish this task(More)
We compared the dynamics of the contraction and relaxation of single myocytes isolated from nontransgenic (NTG) mouse hearts and from transgenic (TG-b-Tm) mouse hearts that overexpress the skeletal isoform of tropomyosin (Tm). Compared with NTG controls, TG-b-Tm myocytes showed significantly reduced maximal rates of contraction and relaxation with no change(More)
About a century ago, Otto Frank in Germany and Ernest Starling in England reported on the relationship between the extent of ventricular filling and pump function of the heart, a phenomenon collectively referred to as FrankStarling's Law of the Heart. Frank's experiments employed the isolated frog heart and suggested that maximum ventricular pressure(More)
The zebrafish serves as a promising transgenic animal model that can be used to study cardiac Ca2+ regulation. However, mechanisms of sarcoplasmic reticulum (SR) Ca2+ handling in the zebrafish heart have not been systematically explored. We found that in zebrafish ventricular myocytes, the action potential-induced Ca2+ transient is mainly (80 %) mediated by(More)
We investigated intracellular localization and substrate specificity of P-activated kinase-1 (Pak1) in rat cardiac myocytes. Pak1 is a serine/threonine protein kinase that is activated by Rac1/Cdc42 and important in signaling of stress responses. Yet the localization and in vivo function of Pak1 in heart cells is poorly understood. Studies reported here(More)
It is becoming clear that upregulated protein kinase C (PKC) signaling plays a role in reduced ventricular myofilament contractility observed in congestive heart failure. However, data are scant regarding which PKC isozymes are involved. There is evidence that PKCmay be of particular importance. Here, we examined PKCquantity, activity, and signaling to(More)
Mutations of cardiac myosin binding protein-C (cMyBP-C) are inherited by an estimated 60 million people worldwide, and the protein is the target of several kinases. Recent evidence further suggests that cMyBP-C mutations alter Ca2+ transients, leading to electrophysiological dysfunction. Thus, while the importance of studying this cardiac sarcomere protein(More)