Current clamp recordings provide more physiologically relevant measurements of ion channel activity (in comparison to voltage clamp), allowing the contribution of different ion channel sub-types to resting membrane potential to be evaluated.

The ICH E14/S7B 2022 Q&As stipulate that in vitro hERG assessments should be conducted in accordance with Good Laboratory Practice (GLP). We present a GLP compliant study using the conventional manual patch-clamp technique in accordance with the ICH E14/S7B Q&A best practice guidelines to establish in-house IC50 values for ondansetron, moxifloxacin and dofetilide.

The recently released ICH E14/S7B 2022 Q&As provides the best practice guidelines for evaluating the effect of preclinical compounds on the human ether-à-go-go-related gene (hERG) potassium channel1.

Eliana is a two-year-old from Canada with a de novo mutation (V434L) in her KCNC1 gene which encodes for the Kv3.1 channel in central nervous system neurons such as cerebellar neurons and GABAergic interneurons. The mutation manifests as a variety of neurological disorders which can include myoclonic epilepsy and ataxia due to K+ channel mutation, developmental epileptic encephalopathy (DEE), or hypotonia, depending on the specific variant. Although Eliana does not exhibit typical DEE, she suffers from hypotonia, cortical-visual impairment, vertical nystagmus, and global delays.

The endo-lysosomal system is a series of intracellular organelles responsible for recycling and degradation of macromolecules. Endo-lysosomes express several functionally diverse ion channels, crucial for regulating organelle trafficking and intracellular signalling as well as maintaining the acidic luminal pH for optimal enzymatic activity. Dysfunctions within the endo-lysosomal system are associated with multiple disorders including lysosomal storage disorders and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Lysosomal ion channels have therefore gained significant attention as potential targets for novel therapeutics.

Lysosomes are a critical component of eukaryotic cells, playing a role in degradation and recycling processes, signal transduction and extracellular secretion(I). Ion channels expressed on the endo-lysosomal membrane are crucial in intracellular signalling and maintaining the acidic luminal pH for optimal hydrolase activity(II). There are a number metabolic disorders, known as lysosomal storage diseases, that arise from lysosomal dysfunction(III).

The dF508 mutation represents the most common cause underlying cystic fibrosis. The resultant misfolding of the nascent cystic fibrosis transmembrane regulator (CFTR) protein and its subsequent proteasomal degradation lead to a deficiency in functional CFTR channels and Cl- efflux at the apical cell membrane in ducts throughout the body (Veit et al. 2016).

Here we share a short video introducing Metrion’s expanded high throughput screening capabilities. To learn more, or to request a quote, please email info@metrionbiosciences.com

The development of Automated Patch Clamp (APC) technology over the last 20 years has
transformed the research and development process for identifying novel drugs for ion channel targets.

Here we share a short video introducing Metrion’s extensive suite of cardiac safety screening services. To learn more, or to request a quote, please email info@metrionbiosciences.com