Researchers use honeybee venom toxin to develop a new tool for studying hypertension

Sep 17, 2008

Researchers at the University of Pennsylvania School of Medicine have modified a honeybee venom toxin so that it can be used as a tool to study the inner workings of ion channels that control heart rate and the recycling of salt in kidneys. In general, ion channels selectively allow the passage of small ions such as sodium, potassium, or calcium into and out of the cell.

The study, published in the Proceedings of the National Academy of Sciences, is from the laboratory of Zhe Lu, M.D, Ph.D., Professor of Physiology and a Howard Hughes Medical Institute Investigator, who looked at the action of a natural bee toxin on inward-rectifier potassium channels, Kir channels for short, to identify new approaches to treat cardiovascular disease.

The honeybee venom toxin, called tertiapin, or TPN, stops the flow of potassium ions across cell membranes by plugging up the opening of Kir channels on the outside of cells. Kir channels in kidneys are potential new targets for treating hypertension. "The clue comes from patients with genetic defects in these channels who lose a lot of sodium because it cannot be effectively reabsorbed and thus have low blood pressure," notes Lu. "An inhibitor specifically against these kidney channels will allow this idea to be tested."

Developing a specific inhibitor for one type of Kir channel has been challenging because the target site is very similar among different types of Kir channels. For example, while TPN inhibits Kir type 1 channels in kidney cells, it also inhibits other types of Kir channels in heart cells. After more than a decade, Lu and his colleagues succeeded in bioengineering a TPN that selectively inhibits Kir channels important for salt recycling in kidneys.

By introducing two mutations into TPN, they engineered a variant, called TPNLQ, which stems the flow of potassium ions in renal Kir type 1 channels at low concentrations, and with a 250-fold sensitivity over six other types of Kir channels.

The development of TPNLQ demonstrates that a highly specific inhibitor of potassium channels can be engineered. TPNLQ can now be used as a tool to prove the concept, in animal studies, that reducing salt reabsorption by plugging up renal Kir type 1 potassium channels is a potential new way to treat hypertension.

Source: University of Pennsylvania

Explore further: Growing a blood vessel in a week

add to favorites email to friend print save as pdf

Related Stories

Russia turns back clocks to permanent Winter Time

14 hours ago

Russia on Sunday is set to turn back its clocks to winter time permanently in a move backed by President Vladimir Putin, reversing a three-year experiment with non-stop summer time that proved highly unpopular.

UN climate talks shuffle to a close in Bonn

14 hours ago

Concern was high at a perceived lack of urgency as UN climate negotiations shuffled towards a close in Bonn on Saturday with just 14 months left to finalise a new, global pact.

Microsoft beefs up security protection in Windows 10

18 hours ago

What Microsoft users in business care deeply about—-a system architecture that supports efforts to get their work done efficiently; a work-centric menu to quickly access projects rather than weather readings ...

Comet Siding Spring whizzes past Mars (Update)

Oct 19, 2014

A comet the size of a small mountain and about as solid as a pile of talcum powder whizzed past Mars on Sunday, dazzling space enthusiasts with the once-in-a-million-years encounter.

Recommended for you

Growing a blood vessel in a week

Oct 24, 2014

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

Oct 24, 2014

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments : 0