School of Biosciences, Cardiff University, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, UK.
Published: September 2018
AI Article Synopsis
Article Abstract
Kv7 channels determine the resting membrane potential of neurons and regulate their excitability. Even though dysfunction of Kv7 channels has been linked to several debilitating childhood neuronal disorders, the ontogeny of the constituent genes, which encode Kv7 channels (KNCQ), and expression of their subunits have been largely unexplored. Here, we show that developmentally regulated expression of specific KCNQ mRNA and Kv7 channel subunits in mouse and human striatum is crucial to the functional maturation of mouse striatal neurons and human-induced pluripotent stem cell-derived neurons. This demonstrates their pivotal role in normal development and maturation, the knowledge of which can now be harnessed to synchronise and accelerate neuronal differentiation of stem cell-derived neurons, enhancing their utility for disease modelling and drug discovery.
Rare and common genetic variants contribute to the risk of atrial fibrillation (AF). Although ion channels were among the first AF candidate genes identified, rare loss-of-function variants in structural genes such as have also been implicated in AF pathogenesis partly by the development of an atrial myopathy, but the underlying mechanisms are poorly understood. While truncating variants (tvs) have been causally linked to arrhythmia and cardiomyopathy syndromes, the role of missense variants (mvs) remains unclear.
Seizure is among the most severe FDA black box warnings of neurotoxicity reported on drug labels. Gaining a better mechanistic understanding of off-targets causative of seizure will improve identification of potential seizure risks preclinically. In the present study, we evaluated an in vitro panel of 9 investigational (Cav2.
Zotepine is a second-generation antipsychotic that demonstrates significant efficacy in antagonizing D and 5-HT receptors. Although clinical investigations have shown that administering zotepine is associated with an increased prevalence of hyperglycemia and a heightened risk of cardiovascular disease, the side effects of zotepine on voltage-gated K (Kv) channels have not been established. Zotepine suppressed the vascular Kv channels in rabbit coronary arterial smooth muscle cells in a concentration-dependent manner, with an IC of 5.
Background And Purpose: Paracetamol has been found to alleviate inflammatory pain by modulating K7 channels. Its metabolite N-acetyl-4-benzoquinoneimine (NAPQI) increases currents through these channels via a stretch of three cysteine residues in the channel S2-S3 linker. Through this effect, the excitability of neurons in the pain pathway is dampened.
* The review discusses the physiological roles of K7.4 and K7.5 channels and recent progress in developing selective modulators that could lead to innovative treatments for hypertension.
* Although research has mainly targeted K7.2 and K7.3 channels, there’s a growing need to explore K7.4 and K7.5 for specific, safe, and effective new compounds to enhance blood pressure control in the future.
