Research at CPC-M - Ion channels – points of attack for drugs against pathological changes in the lungs

Research at CPC-M

Ion channels – points of attack for drugs against pathological changes in the lungs

What happens in the cells of the lung in diseases such as hypertension, edema or fibrosis?

The research group at the Walther Straub Institute for Pharmacology and Toxicology at the Ludwig-Maximilians-Universität (LMU) Munich is investigating this. To this end, it examines specific cell target structures: the family of TRP cation channels.
TRP proteins are ion channels that ensure the transmission of electrically charged particles (ions). Without these channels, positively charged potassium, sodium or calcium ions would not be able to cross the cell membrane. TRP channels play an important role in the perception of taste, temperature or pain.

What happens if these ion channels are either blocked or activated? How does this affect the physiology of the organ system of the lung?

The group is initially investigating this in the mouse model and later also in the patient. The first results: 

TRP channel, graphic
© Alexander Dietrich, LMU München

The blocking of TRPC6 could also have a positive effect on lung transplantation. During the transport from the donor to the recipient, the organ, the isolated lung, is not supplied with blood, which often leads to fatal water retention (edema) during the subsequent transplantation.

In the mouse model, however, TRPC6 blockers in isolated lungs were able to prevent this damage. If they were introduced into donor lungs during transport, the number of fatal transplants could be reduced.

A further discovery: After injuries to the lungs, so-called myofibroblasts, which are formed from the body's own fibroblasts, migrate into the injured tissue during repair processes. Massive invasion of these cells (pulmonary fibrosis) irreversibly damages the lung tissue and prevents gas exchange, so that ultimately only a lung transplantation can help. During the transformation of fibroblasts into myofibroblasts, TRPC6 channel is produced, which promotes this process. Therefore, mice without this ion channel are partially protected from experimental pulmonary fibrosis. 

The next step: Investigation of further subfamilies of TRP channels

While the TRPC6 research group has already been able to conduct successful first experiments with channel activators and inhibitors (blocking agents), many other TRP channels in the lung still lack agents that need to be characterized and tested. 

Many TRP channels such as TRPA1, TRPV4 and TRPM2 are active in the lung tissue, the lung epithelium. They could serve as sensors for toxic substances in the lungs. The relevant channels shall now be identified. They shall then serve as target structures for drugs that can prevent or better heal toxic lung damage in the future.