Description:

Department of Pharmacology Lecture Series on Biochemical and Biophysical Techniques

Carlos G. Vanoye, Ph.D.
Research Associate Professor
Department of Pharmacology
Feinberg School of Medicine

Abstract:

The widespread use of genetic and genomic testing in research and clinical medicine has led to explosive growth in the number of gene variants associated with human diseases and in reference populations. For example, in genetic arrhythmia and epilepsy, 2 diseases studied by our group, there are ~3000 potassium and sodium ion channel variants associated with these diseases. The standard approach for determining the functional properties and the likely pathogenicity of an ion channel variant is cellular electrophysiology using manual patch-clamp recording of heterologously expressed recombinant channels. However, this method is tedious, time- and labor-intensive, making it too low throughput for determining the ever-increasing number of ion channel variants. To overcome this challenge, we have implemented a workflow that combines high efficiency electroporation to achieve transient co-expression of ion channel subunits in cultured cells with automated planar patch clamp recording performed in a 384-well format. Our results indicate that automated electrophysiology is a valid platform for the rapid functional assessment of ion channel variants that allows linking genotype to function for human ion channels and creates new opportunities for precision medicine.