AsianScientist (Mar. 1, 2018) – Researchers from Tohoku University in Japan have developed a device to screen drugs for heart-related side effects. They published their findings in Scientific Reports.
Ion channels are pores made of proteins that exist in some cell membranes, like in cardiac muscle cells. They open and close to allow ions to pass through, creating an electrical signal. Some drugs have side effects by acting on these ion channels. For example the antihistamine astemizole, which has now been withdrawn from the US market, can shut down a potassium ion channel involved in regulating the heartbeat. Taking this drug could lead to irregular palpitations.
Scientists have been investigating ways to screen drugs for side effects on ion channels. In one method, stem cells are directed to transform into cardiac muscle cells that have the specific type of ion channel being targeted for drug testing. This method, however, is tedious and can take up to 90 days of preparation. Other, less time-consuming methods involve inserting ion channels into artificially formed lipid membranes covering a small hole made in a micro- or nano-sized chip. Such methods lead to the formation of unstable membranes, reducing their efficiency during experiments.
In this study, researchers led by Professor Ayumi Hirano-Iwata of Tohoku University’s Advanced Institute of Materials Research fabricated three silicon chips with differently-shaped holes and compared their ability to host ion-channel-containing lipid membranes. Each chip was made of a thick layer of silicon covered by a thin layer of silicon nitride, followed by a thin layer of silicon oxide.
In a series of steps, the central part of the chip was etched away to create a tiny hole. The shape of the hole varied very slightly depending on the type of acid used to dissolve the material. The team found that holes with a gradually tapering edge allowed the formation of the most stable lipid membranes.
The team then added a cell-free synthesized cardiac muscle ion channel, called hERG, to the membranes by centrifugation. They succeeded in detecting electrical currents from the channels and in blocking the currents by administering the drug astemizole, which has a well-recognized adverse effect on hERG channels in the heart.
“This could serve as a new screening platform for assessing the potential risks of drug side effects acting on hERG channels of patients,” said the researchers.
The article can be found at: Tadaki et al. (2017) Mechanically Stable Solvent-free Lipid Bilayers in Nano- and Micro-tapered Apertures for Reconstitution of Cell-free Synthesized hERG Channels.
———
Source: Tohoku University; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
