Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bacterial genes boost current in human cells

19.10.2016

Borrowing and tweaking bacterial genes to Enhance electrical activity might treat heart, nervous system injury

Duke University biomedical engineers have harvested genes for ion channels from bacteria that, with a few tweaks, can create and enhance electrical signaling in human cells, making the cells more electrically excitable.


A red line races across the screen as electrical signals are passed from cell to cell in a straight line. The panel at left shows the slowness of the signals in untreated, electrically inactive cells. The right panel shows the speed gained by treating the cells with a trio of bacterial genes to enhance conductivity.

Credit: Nenad Bursac, Duke University

The technique could one day be used to treat cardiac arrhythmia or to restore electrical functions to scarred heart or nervous system tissues. It might also prove useful for treating a variety of genetic diseases involving poor conductivity in human sodium and calcium channels.

The study appears online in Nature Communications on October 18.

In mammals, the genes controlling the sodium ion channels responsible for a cell's electrical activity are surprisingly large. Too large, unfortunately, to be readily delivered to cells through a virus -- standard procedure in modern gene therapy techniques.

To skirt this size issue, the Duke team delivered smaller ion channels engineered from bacterial genes to primary human cells in a laboratory setting. With the replacement channels, cells that don't normally produce electrical signals became electrically active, and cells that normally produce signals did so more strongly.

"In current medical practice, there is nothing that can be done to stably augment the electrical excitability of cells in the heart or brain," said Nenad Bursac, professor of biomedical engineering at Duke. "There are no drugs that can efficiently do it, and any mammalian genes that might help are too large for gene therapy applications. Our technique, however, uses much smaller bacterial ion channels that proved successful in human cells in the laboratory. We're currently testing this in live animals."

While bacterial genes encoding sodium channels are different than their human counterparts, evolution has conserved many similarities of ion channel design since multi-celled animals diverged from bacteria hundreds of millions of years ago.

Hung Nguyen, a doctoral student in Bursac's laboratory, mutated these bacterial genes so that channels they encode could become active in human cells.

In one experiment, the researchers placed cultured cells in several parallel lines, alternating between electrically active and inactive cells. When stimulated at one end, the electrical signal traveled across the lines very slowly.

The researchers then delivered three genes to the electrically inactive cells: one bacterial gene for a sodium ion channel and two supporting genes encoding a potassium channel and connexin-43, a protein that helps shuttle electrical signals between cells.

When delivered to unexcitable cells taken from the skin, heart and brain, the trio of genes caused the cells to become electrically active, speeding up the electrical signals as they raced across the lines.

"You could imagine using this to alter electrically dead cardiac scar tissue after a heart attack to bridge gaps between healthy cells," said Nguyen, who also points out that all three genes are small enough to be delivered simultaneously by a single virus.

Nguyen and Bursac also showed that the gene encoding the bacterial sodium channel could, by itself, enhance the excitability of cells that are already electrically active. In a second experiment, they delivered the sodium channel gene to cardiomyocytes -- electrically active heart cells -- in conditions mimicking various diseases or stressful situations, such as a heart attack.

"In those pathological conditions, these cells become electrically silent," said Bursac. "But when we add the bacterial channel, we can keep them conducting electrical signals under more severe conditions."

Nguyen adds that this work contributes to a growing body of research that is looking to so-called "primitive" organisms for help with our own health.

"There's a large pool of bacterial species whose sodium channels might have slightly different electrical characteristics to draw from," said Nguyen. "These channels can be also modified to pass calcium ions. We're developing a framework for others to begin exploring these opportunities."

"I think this work is really exciting," said Bursac. "We're basically borrowing from bacteria to eventually help humans suffering from heart or brain diseases."

###

This work was supported by an American Heart Association Predoctoral Fellowship (PRE 16790012) and the National Institutes of Health (HL104326, HL132389, HL126524, HL126193).

CITATION: "Engineering prokaryotic channels for control of mammalian tissue excitability," Hung X. Nguyen, Robert D. Kirkton, and Nenad Bursac. Nature Communications, Online Oct. 18, 2016. DOI: 10.1038/NCOMMS13132

Media Contact

Ken Kingery
ken.kingery@duke.edu
919-660-8414

 @DukeU

http://www.duke.edu 

Ken Kingery | EurekAlert!

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>