Background Understanding the relations between the architecture of myocardial fibers, the spread of excitation, and the associated ECG signals is necessary for addressing the forward problem of electrocardiography, that is, predicting

In non-excitable cells, many agonists increase the intracellular Ca# + concentration ([Ca# + ] i ) by inducing an inositol 1,4,5-trisphosphate (IP $ )-mediated Ca# + release from the intracellular stores. Ca# + influx from the extracellular medium may then sustain the Ca# + signal. [Ca# + ] i recovers its resting level as a consequence of Ca# + -removing mechanisms, i.e. plasma-membrane Ca# + -ATPase (PMCA) pump, Na + \Ca# + exchanger (NCX) and sarco-endoplasmic reticulum Ca# + -ATPase (SERCA) pump. In a study performed in pancreatic acinar cells, evidence has been provided suggesting that, during the decay phase of the agonistevoked Ca# + transients, the Ca# + concentration within the intracellular stores remains essentially constant [Mogami, Tepikin and Petersen (1998) EMBO J. 17, [435][436][437][438][439][440][441][442]. It was therefore hypothesized that, in such a situation, intracellular Ca# + is not only picked up by the SERCA pump, but is also newly released through IP $ -sensitive Ca# + channels, with the balance between these two processes being approximately null. The main aim of the present work was to test this hypothesis by a different experimental approach. Using cardiac microvascular endothelial cells, we found that inhibition of the SERCA pump has no effect on the time course of agonist-evoked Ca# + transients. This

SAHA attenuates arrhythmias in mdx mice by a mechanism in which Cx remodelling and sodium channel re-expression could play an important role.

No abstract

Ventricular arrhythmias are frequently observed in the elderly population secondary to alterations of electrophysiological properties that occur with the normal aging process of the heart. However, the underlying mechanisms remain poorly understood. The aim of the present study was to determine specific age-related changes in electrophysiological properties and myocardial structure in the ventricles that can be related to a structural-functional arrhythmogenic substrate. Multiple unipolar electrograms were recorded in vivo on the anterior ventricular surface of four control and seven aged rats during normal sinus rhythm and ventricular pacing. Electrical data were related to morphometric and immunohistochemical parameters of the underlying ventricular myocardium. In aged hearts total ventricular activation time was significantly delayed (QRS duration: +69%), while ventricular conduction velocity did not change significantly compared with control hearts. Moreover, ventricular activation patterns displayed variable numbers of epicardial breakthrough points whose appearance could change with time. Morphological analysis in aged rats revealed that heart weight and myocyte transverse diameter increased significantly, scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium, and gap junction connexin expression decreased significantly in ventricular myocardium compared with control rats. Our results show that in aged hearts delayed total ventricular activation time and abnormal activation patterns are not due to delayed myocardial conduction and suggest the occurrence of impaired impulse propagation through the conduction system leading to uncoordinated myocardial excitation. Impaired interaction between the conduction system and ventricular myocardium might create a potential reentry substrate, contributing to a higher incidence of ventricular arrhythmias in the elderly population.