15 September 2021

LiU researchers have used high-throughput electrophysiology experiments with a borrowed machine to see how ion channels in cells are influenced by drugs. The highly efficient experiments are a new collaboration with the biotech industry.

Male and female researchers sitting in lab + machine Qpatch 48..
Fredrik Elinder and Nina Ottosson Photographer: Ulrik Svedin
The speed at which experiments can be conducted is important when it is necessary to examine carefully many individual cells, to investigate how a drug affects a specific ion channel on the cell surface. Examples of the drugs examined are those used to treat depression, heart disease or epilepsy.

Photo credit Ulrik Svedin

More rapidly

“We have been able to get good results more rapidly with a machine from the pharmaceuticals industry. This machine has proved to be very useful within academic research”, say Professor Fredrik Elinder and Nina Ottosson, principal research engineer in the Division of Neurobiology (NEURO).

Pipette with Qpatch48 machine.Pipette with Qpatch28. Photo credit Ulrik SvedinNina Ottosson contacted the Sophion Biosciences company in Copenhagen, which has designed the machines and manufactures them. Molecules developed at LiU were first tested in the factory in Denmark. But the scientists have now installed the machine, QPatch II, at the University Hospital Campus in Linköping.

“Initially, we’re talking about a six-month loan. And we’ve applied for a grant from the Swedish Research Council that will allow us to purchase it. It enables us to carry out experiments around 48 times more rapidly. Work that normally takes a year can be completed in approximately a week. But the machine does not mean that people will be made redundant. On the contrary, it will enable us to open up new territory”, says Fredrik Elinder.

48 cell at the same time

The research group works with electrophysiology, i.e. measuring the electrical currents and voltages in cells that are fundamental to all life. All the nerve signals in the body, such as those that cause the heart to beat, are electrical signals. They are created by ion channels. which are proteins that create pathways through the cell membrane. The channels open and close, allowing ions to pass through either into or out from the cell.

“We can measure the signal from a whole cell or from an individual ion channel. Normally, we look at one cell after another, extremely slowly and carefully. That’s why this machine is so exciting – it can measure 48 cells at the same time just as carefully”, says Fredrik Elinder.
Photo credit Ulrik Svedin

We are working to develop
a drug against epilepsy  
 


Ion channels play a key role in epilepsy and several other conditions. The nerves

transmit signals at the wrong time. When a sufficient number of electrical charged ions have entered the cell, electrical impulse arises. This is transmitted along a long nerve fibre and stimulates other nerves.

Pine resin

“We are working to develop a drug against epilepsy, and have identified a specific ion channel that we want to influence. Chemists at LiU synthesise the molecules, and we subsequently examine their effects on the ion channel.”

The scientists have identified substances in common pine resin that affect the particular ion channel they are looking to control. The group has developed as many as 250 new molecules from one naturally occurring molecule in the resin.

“These molecules are known as resin acids. They are charged, fatty molecules that sit in the cell close to the ion channel and cause it to open. In this way they can counteract epilepsy”, says Fredrik Elinder.

The researchers have previously used the slow method and measured the effect on one cell at a time.

“We have carried out the experiments in frog eggs that produce the human ion channel. The new machine means that we can instead use human cells in the same way”, says Nina Ottosson.

Photo credit Ulrik Svedin

A national centre

All new drugs, independently of what they are intended to do, must be tested on some specific ion channels. The results of such tests may mean that a complete pharmaceuticals project must be terminated, or that other projects are started, depending on the results. By carrying out the tests at an early stage, researchers can immediately eliminate molecules with an undesired effect.
The researchers at LiU are now planning to start a national centre, not only for research of this type, but also for automatic electrophysiology measurements on cells that can help other scientific projects.
(Translated by George Farrants)

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