Journal Article

Microelectrode Arrays Measure Blocking of Voltage‐Gated Calcium Ion Channels on Supported Lipid Bilayers Derived from Primary Neurons

Withers, Aimee, Martinelli, Eleonora, Hess, Becky M., Owens, Róisín M., Lu, Zixuan, Kallitsis, Konstantinos, Savva, Achilleas, Schierle, Gabriele S. Kaminski, Pappa, Anna‐Maria, Barberio, Chiara, Fernandez‐Villegas, Ana, Wheeler, Alexandra

2024

Overview

Drug studies targeting neuronal ion channels are crucial to understand neuronal function and develop therapies for neurological diseases. The traditional method to study neuronal ion‐channel activities heavily relies on the whole‐cell patch clamp as the industry standard. However, this technique is both technically challenging and labour‐intensive, while involving the complexity of keeping cells alive with low throughput. Therefore, the shortcomings are limiting the efficiency of ion‐channel‐related neuroscience research and drug testing. Here, this work reports a new system of integrating neuron membranes with organic microelectrode arrays (OMEAs) for ion‐channel‐related drug studies. This work demonstrates that the supported lipid bilayers (SLBs) derived from both neuron‐like (neuroblastoma) cells and primary neurons are integrated with OMEAs for the first time. The increased expression of voltage‐gated calcium (CaV) ion channels on differentiated SH‐SY5Y SLBs  compared to non‐differentiated ones is sensed electrically. Also, dose‐response of the CaV ion‐channel blocking effect on primary cortical neuronal SLBs from rats is monitored. The dose range causing ion channel blocking is comparable to literature. This system overcomes the major challenges from traditional methods (e.g., patch clamp) and showcases an easy‐to‐test, rapid, ultra‐sensitive, cell‐free, and high‐throughput platform to monitor dose‐dependent ion‐channel blocking effects on native neuronal membranes. Primary neuron membranes can be isolated and integrated with microelectrode arrays. This is a study using electrochemical impedance spectroscopy for monitoring the neuronal membrane quality and detecting ion channel blockage on the neuron membranes, which could be a novel technique for drug screening and neuroscience research.

• Publisher: John Wiley & Sons, Inc,Wiley,John Wiley and Sons Inc
• Subject: Animals / blebbing / Brain-derived neurotrophic factor / Calcium Channel Blockers - pharmacology / Calcium Channels - metabolism / Cells / Cells, Cultured / Chemistry / Humans / INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY / Lipid Bilayers - chemistry / Lipid Bilayers - metabolism / Lipids / Materials Science / Membranes / microelectrode arrays / Microelectrodes / Microscopy / Neuroblastoma / Neurons / Neurons - drug effects / Neurons - metabolism / Neurosciences / PEDOT:PSS / Proteins / Rats / Science & Technology - Other Topics / Spectrum analysis / supported lipid bilayers / voltage-gated ion channels