Published September 26, 2013
A faculty member in the UB medical school has received a $1.2 million federal grant to study the gating mechanism of a temperature-sensitive ion channel protein found abundantly in peripheral nerve endings.
The research by Feng Qin, associate professor of physiology and biophysics, on the vanilloid receptor TRPV1 could lead to new drugs that target peripheral pain and cause fewer side effects than existing analgesics.
The work is supported by a four-year grant from the National Institute of General Medical Sciences.
Activated by heat or the compound capsaicin, TRPV1 creates “the burning sensation of pain you feel when you touch a hot plate or cut a chili pepper,” Qin explains.
With insights into how the protein’s thermal transient receptor potential (TRP) channel functions, Qin’s studies could prompt the development of novel analgesics to treat such conditions as thermal hyperalgesia due to inflammation, peripheral nerve injury, diabetes and herpes simplex.
Using cutting-edge biophysical techniques, Qin’s research will shed light on how the protein functions at molecular levels and how its ion channels obtain their strong thermal sensitivity.
His team seeks to understand the fundamental mechanisms of temperature-dependent gating through three main experiments.
Using genetic-mutation techniques, the researchers plan to identify the functional domains of TRPV1.
They will test whether the N-terminal domain contributes to temperature sensing, building on their previous research that sought to identify the origin of the protein’s thermal sensitivity.
They also will study the interactions between sensing domains and subunits, and try to delineate how individual subunit thermal-sensing events contribute to channel opening.
The researchers aim to learn about TRPV1’s dynamic thermal sensitivity, Qin says.
“Our results will unravel the complex mechanisms at work,” he says.
In addition, his team will explore how the channel gates control temperature activation, illuminating the protein’s pathway that links thermal sensing with gating.
Key experiments will shed light on these molecular events during the protein’s activation. The research team’s innovative techniques will combine patch-clamp recording from recombinant channels in heterologous expression systems with kinetic analysis and fast-temperature stimulation, Qin notes.
Fast temperature stimulation achieved through infrared laser diode irradiation—a unique technique developed by Qin’s lab—can produce temperature rises in sub-milliseconds.