Ca(2+) elevations are fundamental to cardiac physiology-stimulating contraction and regulating the gene transcription that underlies hypertrophy. How Ca(2+) specifically controls gene transcription on the background of the rhythmic Ca(2+) increases required for contraction is not fully understood. Here we identify a hypertrophy-signaling module in cardiac myocytes that explains how Ca(2+) discretely regulates myocyte hypertrophy and contraction. We show that endothelin-1 (ET-1) stimulates InsP(3)-induced Ca(2+) release (IICR) from perinuclear InsP(3)Rs, causing an elevation in nuclear Ca(2+). Significantly, we show that IICR, but not global Ca(2+) elevations associated with myocyte contraction, couple to the calcineurin (CnA)/NFAT pathway to induce hypertrophy. Moreover, we found that activation of the CnA/NFAT pathway and hypertrophy by isoproterenol and BayK8644, which enhance global Ca(2+) fluxes, was also dependent on IICR and nuclear Ca(2+) elevations. The activation of IICR by these activity-enhancing mediators was explained by their ability to stimulate secretion of autocrine/paracrine ET-1.

Cardiac hypertrophy is a growth response of the heart to increased hemodynamic demand or damage. Accompanying this heart enlargement is a remodeling of Ca 2؉ signaling. Due to its fundamental role in controlling cardiomyocyte contraction during every heartbeat, modifications in Ca 2؉ fluxes significantly impact on cardiac output and facilitate the development of arrhythmias. Using cardiomyocytes from spontaneously hypertensive rats (SHRs), we demonstrate that an increase in Ca 2؉ release through inositol 1,4,5-trisphosphate receptors (InsP 3Rs) contributes to the larger excitation contraction coupling (ECC)-mediated Ca 2؉ transients characteristic of hypertrophic myocytes and underlies the more potent enhancement of ECCmediated Ca 2؉ transients and contraction elicited by InsP3 or endothelin-1 (ET-1). Responsible for this is an increase in InsP 3R expression in the junctional sarcoplasmic reticulum. Due to their close proximity to ryanodine receptors (RyRs) in this region, enhanced Ca 2؉ release through InsP 3Rs served to sensitize RyRs, thereby increasing diastolic Ca 2؉ levels, the incidence of extra-systolic Ca 2؉ transients, and the induction of ECC-mediated Ca 2؉ elevations. Unlike the increase in InsP 3R expression and Ca 2؉ transient amplitude in the cytosol, InsP3R expression and ECC-mediated Ca 2؉ transients in the nucleus were not altered during hypertrophy. Elevated InsP 3R2 expression was also detected in hearts from human patients with heart failure after ischemic dilated cardiomyopathy, as well as in aortic-banded hypertrophic mouse hearts. Our data establish that increased InsP 3R expression is a general mechanism that underlies remodeling of Ca 2؉ signaling during heart disease, and in particular, in triggering ventricular arrhythmia during hypertrophy.calcium ͉ ECC ͉ IP3 ͉ SHR ͉ signalling

Radiofrequency (RF)-related heating of cardiac pacemaker leads is a serious concern in magnetic resonance imaging (MRI).

The purpose of this study was to assess the distribution of RF-induced E-fields inside a gel-filled phantom of the human head and torso and compare the results with the RF-induced temperature rise at the tip of a straight conductive implant, specifically examining the dependence of the temperature rise on the position of the implant inside the gel. MRI experiments were performed in two different 1.5T MR systems of the same manufacturer. E-field distribution inside the liquid was assessed using a custom measurement system. The temperature rise at the implant tip was measured in various implant positions and orientations using fluoroptic thermometry. The results show that local E-field strength in the direction of the implant is a critical factor in RF-related tissue heating. The actual E-field distribution, which is dependent on phantom/ body properties and the MR-system employed, must be considered when assessing the effects of RF power deposition in implant safety investigations. Magn Reson Med 60:312-319, 2008.

Pharmacological S1P receptor agonists have distinct effects on ischaemia-reperfusion injury. Their efficacy when applied during reperfusion makes them potential candidates for pharmaceutical postconditioning therapy after cardiac ischaemia.