"Eventless" InsP 3 -dependent SR-Ca 2+ Release Affecting Atrial Ca 2+ Sparks

Augmented inositol 1,4,5-trisphosphate receptor (InsP3R) function has been linked to a variety of cardiac pathologies, including cardiac arrhythmia. The contribution of inositol 1,4,5-trisphosphate-induced Ca2+ release (IP3ICR) in excitation-contraction coupling (ECC) under physiological conditions, as well as under cellular remodelling, remains controversial. Here we test the hypothesis that local IP3ICR directly affects ryanodine receptor (RyR) function and subsequent Ca2+-induced Ca2+ release in atrial myocytes. IP3ICR was evoked by UV-flash photolysis of caged InsP3 under whole-cell configuration of the voltage-clamp technique in atrial myocytes isolated from C57/BL6 mice. Photolytic release of InsP3 was accompanied by a significant increase in the Ca2+ release event frequency (4.14±0.72 vs. 6.20±0.76 events (100 μm)−1 s−1). These individual photolytically triggered Ca2+ release events were identified as Ca2+ sparks, which originated from RyR openings. This was verified by Ca2+ spark analysis and pharmacological separation between RyR and InsP3R-dependent sarcoplasmic reticulum (SR)-Ca2+ release (2-aminoethoxydiphenyl borate, xestospongin C, tetracaine). Significant SR-Ca2+ flux but eventless SR-Ca2+ release through InsP3R were characterized using SR-Ca2+ leak/SR-Ca2+ load measurements. These results strongly support the idea that IP3ICR can effectively modulate RyR openings and Ca2+ spark probability. We conclude that eventless and highly efficient InsP3-dependent SR-Ca2+ flux is the main mechanism of functional cross-talk between InsP3Rs and RyRs, which may be an important factor in the modulation of ECC sensitivity.

Une solidarité franco-allemande en Suisse au coeur de la première guerre : Stefan Zweig (1881-1942) et Romain Rolland (1866-1944)

Stefan Zweig arrive en Suisse en novembre 1917. D’abord libéré du service militaire pour deux mois, il obtient finalement la permission de rester en Suisse jusqu’à la fin de la guerre. Il peut ainsi assister aux répétitions et à la première de Jérémie, sa pièce de théâtre pacifiste représentée pour la première fois au Stadttheater de Zurich en février 1918. Son séjour en Suisse est également marqué par le développement de son admiration et de son amitié pour Romain Rolland – celui qu’il désigne comme étant « la conscience morale de l’Europe ». L’objet de cet article est de montrer que la conjonction Suisse–Rolland a joué un rôle absolument essentiel dans la vie personnelle et créatrice de Zweig.