"If nicotine activated ACh receptors found in muscle as potently as it does brain ACh receptors, smoking would cause intolerable and perhaps fatal muscle contractions."
The authors find that extremely subtle differences between these nearly identical receptors, which both respond the same way to their intended messenger, namely ACh, make that nicotine can mimic the non-covalent interactions of ACh with the brain receptor, but not with the muscular one. Specifically, it's one hydrogen bond and one interaction between pi electrons and a cation which are to blame for the difference.
While it is not yet clear why and how nicotine causes addiction, researchers believe this goes via such ACh receptors, and specifically via the receptor type that Xiu et al have studied.
Now what I find intriguing is that many people (like me, for instance) don't get addicted to nicotine. I rather enjoy the sensual experience of a good tobacco, but I can take it or leave it at any time, and as there is no place left in this world where one can enjoy it, I end up leaving it. It may be genetic, as my parents have similar experience.
So does this new research mean that I (and non-addicted people like me) have a more muscle-like ACh receptor in my brain ? In the post genome age this should be really easy to answer. And if this addiction effect depends on such extremely subtle and weak interactions, wouldn't it be easy to disrupt this and stop the addiction from happening (well, OK, I know we don't want to interfere with the ACh's natural interaction, so it may be tricky)? I tend to think that if people had really tried to solve this problem, rather than terrorising the people affected by it, it would have been sorted out by now.