This paper considers whether the population of known transiting exoplanets provides evidence for additional outer planets on inclined orbits, due to the perturbing effect of such planets on the orbits of inner planets. As such, we develop a semi-analytical method for calculating the probability that two mutually inclined planets are observed to transit. We subsequently derive a simplified analytical form to describe how the mutual inclination between two planets evolves due to secular interactions with a wide orbit inclined planet and use this to determine the mean probability that the two inner planets are observed to transit. From application to Kepler-48 and HD-106315 we constrain the inclinations of the outer planets in these systems (known from RV). We also apply this work to the so called Kepler Dichotomy, which describes the excess of single transiting systems observed by Kepler. We find 3 different ways of explaining this dichotomy: some systems could be inherently single, some multi-planet systems could have inherently large mutual inclinations, while some multi-planet systems could cyclically attain large mutual inclinations through interaction with an inclined outer planet. We show how the different mechanisms can be combined to fit the observed populations of Kepler systems with one and two transiting planets. We also show how the distribution of mutual inclinations of transiting two planet systems constrains the fraction of two planet systems that have perturbing outer planets, since such systems should be preferentially discovered by Kepler when the inner planets are coplanar due to an increased transit probability.

This paper considers secular interactions within multi-planet systems. In particular we consider dynamical evolution of known planetary systems resulting from an additional hypothetical planet on an eccentric orbit. We start with an analytical study of a general two-planet system, showing that a planet on an elliptical orbit transfers all of its eccentricity to an initially circular planet if the two planets have comparable orbital angular momenta. Application to the single Super-Earth system HD38858 shows that an additional hypothetical planet below current radial velocity (RV) constraints with Msini=3-10M ⊕ , semi-major axis 1-10au and eccentricity 0.2-0.8 is unlikely to be present from the eccentricity that would be excited in the known planet (albeit cyclically). However, additional planets in proximity to the known planet could stabilise the system against secular perturbations from outer planets. Moreover these additional planets can have an Msini below RV sensitivity and still affect their neighbours. For example, application to the two Super-Earth system 61Vir shows that an additional hypothetical planet cannot excite high eccentricities in the known planets, unless its mass and orbit lie in a restricted area of parameter space. Inner planets in HD38858 below RV sensitivity would also modify conclusions above about excluded parameter space. This suggests that it may be possible to infer the presence of additional stabilising planets in systems with an eccentric outer planet and an inner planet on an otherwise suspiciously circular orbit. This reinforces the point that the full complement of planets in a system is needed to assess its dynamical state.

Atrial arrhythmias, such as atrial fibrillation (AF), are a major mortality risk and a leading cause of stroke. The IP3 signalling pathway has been proposed as an atrial-specific target for AF therapy, and atrial IP3 signalling has been linked to the activation of calcium sensitive adenylyl cyclases AC1 and AC8. We investigated the involvement of AC1 in the response of intact mouse atrial tissue and isolated guinea pig atrial and sino-atrial node (SAN) cells to the α-adrenoceptor agonist phenylephrine (PE) using the selective AC1 inhibitor ST034307. The maximum rate change of spontaneously beating mouse right atrial tissue exposed to PE was reduced from 14.5% to 8.2% (p = 0.005) in the presence of 1 μM ST034307, whereas the increase in tension generated in paced left atrial tissue in the presence of PE was not inhibited by ST034307 (Control = 14.2%, ST034307 = 16.3%; p > 0.05). Experiments were performed using isolated guinea pig atrial and SAN cells loaded with Fluo-5F-AM to record changes in calcium transients (CaT) generated by 10 μM PE in the presence and absence of 1 μM ST034307. ST034307 significantly reduced the beating rate of SAN cells (0.34-fold decrease; p = 0.003) but did not inhibit changes in CaT amplitude in response to PE in atrial cells. The results presented here demonstrate pharmacologically the involvement of AC1 in the downstream response of atrial pacemaker activity to α-adrenoreceptor stimulation and IP3R calcium release.

Atrial arrhythmias, such as atrial fibrillation (AF), are a major mortality risk and a leading cause of stroke. The IP3 signalling pathway has been proposed as an atrial specific target for AF therapy, and atrial IP3 signalling has been linked to the activation of calcium sensitive adenylyl cyclases AC1 and AC8. Here we investigated the involvement of AC1 in the response of intact mouse atrial tissue and isolated guinea pig atrial and sinoatrial node (SAN) cells to the α-adrenoceptor agonist phenylephrine (PE) using the selective AC1 inhibitor ST034307. The maximum rate change of spontaneously beating mouse right atrial tissue exposed to PE was reduced from 14.46 % to 8.17% (P = 0.005) in the presence of 1 μM ST034307, whereas the increase in tension generated in paced left atrial tissue in the presence of PE was not inhibited by ST034307 (Control = 14.20 %, ST034307 = 16.32 %; P > 0.05). Experiments were performed using isolated guinea pig atrial and SAN cells loaded with Fluo-5F-AM to record changes in calcium transient amplitude (CaT) generated by 10μM PE in the presence and absence of 1μM ST034307. ST034307 significantly reduced the beating rate of SAN cells (0.34-fold decrease; P = 0.004), but did not result in an inhibition of CaT amplitude increase in response to PE in atrial cells. The results presented here demonstrate the involvement of AC1 in the downstream response of atrial pacemaker activity to α-adrenoreceptor stimulation and IP3R calcium release.