# Veratridine-Induced Oscillations in Nav 1.7 but Not Nav 1.5 Sodium Channels Are Revealed by Membrane Potential Sensitive Dye

## TL;DR

This study uses a fluorescent dye to observe how different sodium channels respond to a drug, revealing unique behaviors in pain-related channels.

## Contribution

A new method to distinguish sodium channel isoforms using fluorescent dye and drug-induced oscillations is introduced.

## Key findings

- Nav 1.5 channels show a slow, steady fluorescence increase when activated by veratridine.
- Nav 1.7 channels display rapid fluorescence rise and oscillatory behavior under the same conditions.
- Oscillations in Nav 1.7 are confirmed to be sodium channel-dependent via drug inhibition.

## Abstract

Voltage-gated sodium channels (Navs) are critical for membrane potential depolarisation in cells, with especially important roles in neuronal and cardiomyocyte membranes. Their malfunction results in a range of disorders, and they are the target of many widely used drugs. A rapid yet accurate functional assay is therefore desirable both to probe for novel active compounds and to better understand the many different Nav isoforms. Here, we use fluorescence to monitor Nav function: cells expressing either the cardiac Nav 1.5 or pain-associated Nav 1.7 were loaded with fluorescent membrane potential sensitive dye and then stimulated with veratridine. Cells expressing Nav 1.5 show a concentration-dependent slow rise and then a plateau in fluorescence. In contrast, cells expressing Nav 1.7 show a more rapid rise and then unexpected oscillatory behavior. Inhibition by flecainide and mexiletine demonstrates that these oscillations are Nav-dependent. Thus, we show that this fluorescent membrane potential dye can provide useful functional data and that we can readily distinguish between these two Nav isoforms because of the behavior of cells expressing them when activated by veratridine. We consider these distinct behaviors may be due to different interactions of veratridine with the different Nav isoforms, although more studies are needed to understand the mechanism underlying the oscillations.