Rescuing cardiac automaticity in L-type Cav1.3 channelopathies and beyond.

Pacemaker activity of the sino-atrial node generates the heart rate. Disease of the sinus node and impairment of atrioventricular conduction induce an excessively low ventricular rate (bradycardia), which cannot meet the needs of the organism. Bradycardia accounts for about half of the total workload of clinical cardiologists. The 'sick sinus' syndrome (SSS) is characterized by sinus bradycardia and periods of intermittent atrial fibrillation. Several genetic or acquired risk factors or pathologies can lead to SSS. Implantation of an electronic pacemaker constitutes the only available therapy for SSS. The incidence of SSS is forecast to double over the next 50 years, with ageing of the general population thus urging the development of complementary or alternative therapeutic strategies. In recent years an increasing number of mutations affecting ion channels involved in sino-atrial automaticity have been reported to underlie inheritable SSS. L-type Cav 1.3 channels play a major role in the generation and regulation of sino-atrial pacemaker activity and atrioventricular conduction. Mutation in the CACNA1D gene encoding Cav 1.3 channels induces loss-of-function in channel activity and underlies the sino-atrial node dysfunction and deafness syndrome (SANDD). Mice lacking Cav 1.3 channels (Cav 1.3-/- ) fairly recapitulate SSS and constitute a precious model to test new therapeutic approaches to handle this disease. Work in our laboratory shows that targeting G protein-gated K+ (IKACh ) channels effectively rescues SSS of Cav 1.3-/- mice. This new concept of 'compensatory' ion channel targeting shines new light on the principles underlying the pacemaker mechanism and may open the way to new therapies for SSS.

Weak static and extremely low frequency magnetic fields affect in vitro pollen germination.

This study concerns the effects of a weak static magnetic field (MF) at 10 µT oriented downward, combined with a 16-Hz sinusoidal MF (10 µT), on in vitro pollen germination of kiwifruit (Actinidia deliciosa). Extremely low frequency magnetic field (ELF-MF) exposure was carried out by a signal generator unit connected to a copper wire solenoid, inside which samples where placed. Two different kinds of treatment were performed: direct and indirect. In the direct treatment, pollen samples were directly exposed during rehydration, germination, or both. In the indirect treatment, the pollen growth medium was prepared with water aliquots (at standard temperature of 20°C and pH = 6.74) that were exposed before use for 8 or 24 h. The main purpose of our research was to identify a biological marker (in vitro pollen germination in a stressing growth medium without Ca2+) susceptible to the effects of direct or indirect ELF-MF exposure. The working variable was the pollen germination rate, as detected blind after 3 h 30 min by an Axioplan microscope. A directionally consistent recovery of germination percentage was observed both for direct exposure (during germination and both rehydration and germination phases) and water-mediated exposure (with water exposed for 24 h and immediately used). Our results suggest that the ELF-MF treatment might partially remove the inhibitory effect caused by the lack of Ca2+ in the culture medium, inducing a release of internal Ca2+ stored in the secretory vesicles of pollen plasma membrane. Although preliminary, findings seem to indicate the in vitro pollen performance as adequate to study the effects of ELF-MFs on living matter.