In this Research Roundup you can read about knockout (KO) models for cardiology research, the role of acid-sensing channels (ASICs) in chemotherapy resistance, and the glycolysis vs mitochondria energy battle in neurotransmission (and how it’s tied to developmental stage).
Knocking out Nav1.5 in iPSC cardiomyocytes means a new model to study Nav1.5 channel variants and potential new drugs
To better understand how variants in Nav1.5 might affect human hearts, a team from CERVO Brain Research Center (Canada) made an induced pluripotent stem cell line (iPSC) that has the SCN5a gene coding for the cardiac Na+ channel Nav1.5 knocked out via CRISPR-Cas9. They then used this iPSC cell line to create cardiomyocytes (iPSC-CMs) that lack Nav1.5 channels. With the help of some careful electrophysiology and optical mapping to characterize and verify the iPSC-CM’s behavior, the team has created a new model that will help in the diagnosis and treatment of cardiovascular diseases.
Acid-sensing ion channels promote drug resistance in liver cancer through EMT
Specifically, acid-sensing ion channel 1a (ASIC1a) in hepatocellular carcinoma (HCC). Its already know that overexpression of ASIC1a modulates the Ca2+/PI3K/AKT signaling pathway in the extracellular acidic microenvironment, which in turn leads to more drug resistance. But in this new preprint, the researchers show that extracellular acidification through AKT/GSK3β/Snail signaling stimulates epithelial-to-mesenchymal transition (EMT) to make HCC more resistant to treatment. There’s a lot in here, but ASICs could be potential targets to boost chemotherapy.
Anti-ASIC1 Antibody (ASC-014) for western blotting.
Who does the heavy lifting in transmission: glycolysis or mitochondria?
To settle the debate of glycolysis vs mitochondrial oxidative phosphorylation (OxPhos) as the preferred driver of transmission in neurons, scientists from the Reno School of Medicine (US) blocked presynaptic glycolysis or mitochondrial respiration in mice. Using a synapse specialized for sustained high-frequency firing (the calyx of Held) as their model, it turns out that there’s actually a preference for one or the other depending on the developmental stage of the animal.
D-AP5 (D-145) to block NMDA receptors.
(-)-Bicuculline methiodide (B-136) to inhibit GABAA receptors.
QX-314 bromide (Q-100) in a pipette solution following postsynaptic voltage-clamp recordings.
Oligomycin (O-500) as part of a method to block mitochondrial ATP synthesis.
Photo by Joanna Kosinska.