Nicotine in Brain and Muscle Receptors

The nicotine receptors in the brain and muscles are almost exactly identical, so why does nicotine show a much higher affinity for the receptors in the brain than the ones in muscle cells? As it turns out, a single amino acid makes all the difference.

The brain receptor has a lysine molecule near the “box” region of the receptor (the part that actually grabs the incoming molecule), while a muscle receptor sports a glycine molecule. When CalTech scientists removed the muscle receptor’s glycine and replaced it with the lysine molecule, the muscle receptor’s conformation was altered just enough to accept the nicotine molecule.

It is actually a very good thing that nicotine has a low affinity for muscle cells: the body’s response to receiving nicotine in the nicotinic receptors of the neuromuscular junction is to open ion channels and depolarize the muscle cells, causing them to contract. The continued presence of nicotine keeps the ion channels open, preventing the muscle cell from relaxing, effectively paralyzing it. This could cause respiratory paralysis, as has been seen in cases of excessive nicotine levels, beyond that of what one would normally ingest through normal smoking.

This research is interesting because it has implications not just in medical ways to help smokers quit, but in other diseases where receptor problems are suspected or known, such as Alzheimer’s, autism, Parkinson’s and schizophrenia.

http://sciencenow.sciencemag.org/cgi/content/full/2009/302/2

Dee Silverthorn, Human Physiology, An Integrated Approach (4th Ed).