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 Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>