Before we begin, please allow me to apologise for the slight wobble in posting regularity in the past week, we moved house this weekend and so not only did I have to locate and extract my laptop from the box I enthusiastically packed it in without labelling it, I’m also currently without home internet. This means that I can write to my heart’s content but I have to haunt the coffee shops of Staines to get anything online. Everything should be back to normal after this week; in the meantime I hope you’ll be patient with me. If it helps, I can tell you all that my new house is very exciting and will in the future allow me to write in the garden under a tree, which will make me very happy.
When I was younger, I had exercise-induced asthma. This was, on the one hand a reasonable excuse for why I couldn’t run half a mile without wheezing dramatically and turning a fun shade of purple but on the other hand, a little bit irritating. As someone with a mild form of asthma, I was prescribed salbutamol, often better known in the UK by the brand name Ventolin. Being me, as a young teenager I was fascinated by my inhaler, a huge part of me was, once it started working of course, bouncing up and down and shouting “oh my holy wow, it’s like magic air!” and a tiny slightly saner part was thinking “I wonder how it does that?” We’re very used to the idea that we can take a tablet and it will have an effect, but inhalers work differently, the drug is inhaled and gets straight to work in the lungs and airways, it’s no wonder that it seems a little magical, but, as always, it’s all down to some nifty molecules.
Asthma is characterised by inflammation of the airways, there are a huge range of things that can trigger the inflammation of asthma in an individual, but the asthma itself, the effect of wheezing, tight chest and shortness of breath is caused by inflammatory molecules being released. These inflammatory chemicals, once they have been released, cause panic, they yell frantic instructions to the muscles in the airway and tell them to contract, they give orders for mucus to be produced on the double, they generally constrict your airways and make it hard for you to breath. It’s easy to see these inflammatory critters as the bad guys here, but it isn’t really their fault; they’re really good at their job, it’s just that something has caused them to be released at the wrong time, in the wrong place. They’re a SWAT team who have accidentally ended up in a library, causing chaos where none was needed.
Nonetheless, it’s still not ideal if your chest is tight, your breath wheezes through your airways and you can’t catch your breath. You could be forgiven for feeling frustrated with your inappropriately activated SWAT molecules. Luckily, there is a group of molecules in your airways who are responsible for relaxation, in the midst of the chaos caused by the inflammatory response it is these molecules that salbutamol calls upon for aid.
As soon as you inhale salbutamol, it heads straight for beta-2 adrenergic (B2A) receptors in the smooth muscle that lines your airways. B2A is the head of Team Chill Out, a molecule so skilled at relaxation that it could write a book and make millions, if only it could write. And B2A is not alone; it has a team of molecules to help; a soothing group of librarians are here to clear up the mess made by the over-eager SWAT team. When salbutamol binds B2A, it notifies a nearby G-protein, which activates a signalling chain: the G-protein pokes adenylyl cyclase in the ribs, waking it up. It immediately speeds up the formation of the cAMP molecule.
cAMP uses a calcium channel to change the polar charge of the cell by decreasing the amount of positively charged calcium lying around the place. This is crucial because, like nerve cell conduction, muscle contraction is initiated by changes in the cellular charge, and huge volumes of calcium rushing in are what trigger muscles to begin the process of contraction. Reducing the amount of calcium in the area means that muscles are forced to relax instead of contracting. Soothing music plays, and the airways start to relax out of their spasm. Air can start to make it through into the lungs properly, and you stop feeling so breathless and wheezy.
This is how salbutamol helps you breathe again; it acts on the B2A receptor to trigger a signalling cascade that forces your muscles to relax and let air in. Not magic air, after all, then.