A 3D molecular atlas of the chick embryonic heart

We present a detailed analysis of gene expression in the 2-day (HH12) embryonic chick heart. RNA-seq of 13 micro-dissected regions reveals regionalised expression of 15,570 genes. Of these, 132 were studied by in situ hybridisation and a subset (38 genes) was mapped by Optical Projection Tomography or serial sectioning to build a detailed 3-dimensional atlas of expression. We display this with a novel interactive 3-D viewer and as stacks of sections, revealing the boundaries of expression domains and regions of overlap. Analysis of the expression domains also defines some sub-regions distinct from those normally recognised by anatomical criteria at this stage of development, such as a previously undescribed subdivision of the atria into two orthogonal sets of domains (dorsoventral and left-right). We also include a detailed comparison of expression in the chick with the mouse and other species.

Effects of Bepridil on Stretch-Activated BKca Channels and Stretch-Induced Extrasystoles in Isolated Chick Hearts

Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SACNS) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryonic ventricular myocytes were used for single-channel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS, on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKca channels but possibly also blocks SACNS, and thus decreases the stretch-induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential).