It’s crazy to think that we still don’t quite understand the mechanism behind one of the most common medical interventions – general anaesthetic.
But researchers in Australia just got a step closer by discovering that one of the most commonly used anaesthetic drugs doesn’t just put us to sleep; it also disrupts communication between brain cells.
The team investigated the drug propofol, a super-popular option for surgeries worldwide. A potent sedative, the drug is thought to put us to sleep through its effecton the GABA neurotransmitter system, the main regulator of our sleep-and-wake cycles in the brain.
But anyone who’s been “put under” will know that waking up from a general anaesthetic feels rather different from your usual morning grogginess.
On top of that, some people can experience serious side-effects, so scientists have been trying to figure out what else the drugs might be doing in the brain.
Using live neuron cell samples from rats and fruit flies, the researchers were able to track neurotransmitter activity thanks to a super-resolution microscope, and discovered that propofol messes with a key protein that nerve cells use to communicate with each other.
This protein, called syntaxin1A, isn’t just found in animal models – people have it, too.
“Every neuron communicates with other neurons by way of syntaxin1A-mediated neurotransmission, which is highly conserved from worms to humans,” the team writes in the study.
And it looks like the anaesthetic drug puts the brakes on this protein, making otherwise normal brain cell connections sluggish, at least for a while.
“We found that propofol restricts the movement of [syntaxin1A], required at the synapses of all neurons. This restriction leads to decreased communication between neurons in the brain,” says lead author of the study, PhD student Adekunle Bademosi from Queensland Brain Institute (QBI) at the University of Queensland.
The researchers think this disruption could be key to how propofol allows for pain-free surgery to take place – first it knocks us out as a normal sleeping pill would, and then takes things up a notch by disrupting brain connectivity.
The team’s results are a significant step up in what we know about the workings of general anaesthetic – a long-standing medical mystery.
“It is indeed a 180-year-old question, one of the unresolved mysteries in medicine,” senior author of the study, Bruno van Swinderen from QBI.
“I think it has been a hard problem to solve because our hypotheses for explaining general anaesthesia have largely paralleled our growing understanding of how the brain works.”
To be able to track down the movements of a protein in the synapses – the connecting points between nerve cells – scientists needed to know how this synaptic process even works, a discovery that was only awarded a Nobel Prize as recently as 2013.
But now that imaging techniques are advancing, we can likely expect researchers to unravel the anaesthetic mystery even further.
More research will be needed to establish a causal link between propofol’s disruption of the syntaxin1A protein and its anaesthetic effects – and then there are also other anaesthetic drugs to be tested.
Still, van Swinderen thinks it’s possible that all general anaesthetics work in this particular manner, because they all share an important characteristic – they all bind to fats, and fats are found at crucial neurotransmitter exchange points in our synapses.
“The discovery has implications for people whose brain connectivity is vulnerable, for example in children whose brains are still developing or for people with Alzheimer’s or Parkinson’s disease,” says van Swinderen.
“It has never been understood why general anaesthesia is sometimes problematic for the very young and the old. This newly discovered mechanism may be a reason.”