In a new study published in Molecular Biology of the Cell, a team of Rensselaer Polytechnic Institute researchers identified a previously unknown propofol anaesthetic mechanism, which, despite its frequent clinical application, is poorly understood. The study found that propofol exposure impacted the transportation of proteins to the surface of neurons, interrupting their function.
Almost all animal cells, including human cells, are highly compartmentalised and rely on efficient movement of protein material between compartments in vesicles. This transport must be efficient and highly specific to maintain cellular organisation and function.
The research team was led by Dr Marvin Bentley, associate professor at Rensselaer Polytechnic Institute, whose laboratory studies vesicle transport in neurons. Neurons are particularly reliant on vesicle transport because axons, often organised in nerve bundles. can span distances of up to 100cm in humans. Errors in vesicle transport have been linked to neurodevelopmental and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
This new study found that propofol affects a family of proteins called kinesins – small ‘motor proteins’ that move vesicles on tiny filaments called microtubules.
Dr Bentley’s team observed that vesicle movement of two prominent kinesins, Kinesin-1 and Kinesin-3, was substantially reduced in cells exposed to propofol. The team then showed that propofol-induced transport delays led to a significant drop in protein delivery to axons.
“The mechanism by which propofol works is not fully understood,” Bentley said. “What we discovered was unexpected: propofol altered the trafficking of vesicles in live neurons.”
Overall, the research contributes significantly to our understanding of how propofol works. Most studies on propofol’s anaesthetic mechanism have instead focused on its interaction with an ion channel called the GABAA receptor, which inhibits neurotransmission when activated.
This new study demonstrates that vesicle transport is an additional mechanism that may be important for propofol’s anaesthetic effect. Discovery of this new propofol effect has important applications for human health and may lead to the development of better anaesthetic drugs.
Source: Rensselaer Polytechnic Institute
