Dilated cardiomyopathy (DCM) is a multifactorial disease characterized by left ventricular dilation that is associated with systolic dysfunction and increased action potential duration. The Kir2.x K⁺channels (encoded by KCNJ genes) regulate the inward rectifier current (I_K1) contributing to the final repolarization in cardiac muscle. Here, we describe the transitions in the gene expression profiles of 4 KCNJ genes from healthy or dilated cardiomyopathic human hearts. In the healthy adult ventricles, KCNJ2, KCNJ12, and KCNJ4 (Kir2.1–2.3, respectively) genes were expressed at high levels, while expression of the KCNJ14 (Kir2.4) gene was low. In DCM ventricles, the levels of Kir2.1 and Kir2.3 were upregulated, but those of Kir2.2 channels were downregulated. Additionally, the expression of the DLG1 gene coding for the synapse-associated protein 97 (SAP97) anchoring molecule exhibited a 2-fold decline with increasing age in normal hearts, and it was robustly downregulated in young DCM patients. These adaptations could offer a new aspect for the explanation of the generally observed physiological and molecular alterations found in DCM.

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca²⁺ current (I_Ca), late Na⁺ current (I_Na-late), rapid and slow components of the delayed rectifier K⁺ current (I_Kr and I_Ks, respectively), inward rectifier K⁺ current (I_K1), transient outward K⁺ current (I_to1), and Na⁺/Ca²⁺ exchange current (I_NCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of I_K1 and the recovery kinetics of I_to. I_K1 displayed a largely four-fold larger density in canine than human myocytes, and I_to recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger I_K1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

Cannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (I_Kr) and slow (I_Ks) delayed rectifier, the transient outward (I_to) and inward rectifier (I_K1) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased I_Kr, I_Ks and I_to (only in dog) significantly with corresponding estimated EC₅₀ values of 4.9, 3.1 and 5 µM, respectively, without changing I_K1. Although the EC₅₀ value of CBD was found to be higher than literary C_max values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired.

The human voltage gated potassium channel Kv1.5 that conducts the I_Kur current is a key determinant of the atrial action potential. Its mutations have been linked to hereditary forms of atrial fibrillation (AF), and the channel is an attractive target for the management of AF. The development of I_Kur blockers to treat AF resulted in small molecule Kv1.5 inhibitors. The selectivity of the blocker for the target channel plays an important role in the potential therapeutic application of the drug candidate: the higher the selectivity, the lower the risk of side effects. In this respect, small molecule inhibitors of Kv1.5 are compromised due to their limited selectivity. A wide range of peptide toxins from venomous animals are targeting ion channels, including mammalian channels. These peptides usually have a much larger interacting surface with the ion channel compared to small molecule inhibitors and thus, generally confer higher selectivity to the peptide blockers. We found two peptides in the literature, which inhibited I_Kur: Ts6 and Osu1. Their affinity and selectivity for Kv1.5 can be improved by rational drug design in which their amino acid sequences could be modified in a targeted way guided by in silico docking experiments.

In the development of biocompatible synthetic materials for the surgery of bone fractures, open porous Ti foams have a high potential to find application as a geometrically and mechanically adaptable implant matrix. The present state of research mainly focuses on Ti foams produced using powder metallurgy, whereas cast manufacturing is barely investigated despite cast parts achieve higher mechanical strength and durability than those sintered. Therefore, the present study describes the manufacturing of Ti foam by precision casting using a centrifugal casting machine. Experimental investigations employed casting of CP-Ti grade 1 and grade 2 purity, and characteristics of this technique were ascertained and compared with the current proficiency in the field of dental research. The knowledge of specific influences on the feasibility of Ti foam manufacturing by precision casting – collated in this survey – enables specific optimization of the casting process as well as design enhancement relating to the cellular structure.