Smell depends on sensory receptors that respond to airborne chemicals. In humans, these chemoreceptors are located in the olfactory epithelium — a patch of tissue about the size of a postage stamp located high in the nasal cavity. The olfactory epithelium is made up of three kinds of cells:
- sensory neurons each with a primary cilium
- supporting cells between them
- basal cells that divide regularly producing a fresh crop of sensory neurons to replace those that die (and providing an exception to the usual rule that neurons seldom are replaced)
The sequence of events
- The cilia of the sensory neurons are immersed in a layer of mucus. Odorant molecules (molecules that we can smell) dissolve in the mucus.
- These then bind to receptors on the cilia. These are "7-pass" transmembrane proteins.
- Binding of the odorant activates a G protein coupled to the receptor on its cytoplasmic side.
- This activates adenylyl cyclase, an enzyme embedded in the plasma membrane of the cilia.
- Adenylyl cyclase catalyzes the conversion of ATP to the "second messenger" cyclic AMP (cAMP) in the cytosol.
- receptors of peptide hormones
- taste receptors
- the light receptor rhodopsin
- GABAB receptors at certain synapses in the brain
- cAMP opens up ligand-gated sodium channels for the facilitated diffusion of Na+ into the cell
- The influx of Na+ reduces the potential across the plasma membrane.
- If this depolarization reaches threshold, it generates an action potential.
- The action potential is conducted back along the olfactory nerve to the brain.
- The brain evaluates this and other olfactory signals reaching it as a particular odor.
How can one kind of cell enable us to discriminate among so many different odors?
Humans can discriminate between hundreds, perhaps thousands, of different odorant molecules, each with its own structure. How can one kind of cell provide for this?
- The mechanism:
Although a single olfactory neuron contains over a thousand receptor genes, there is only a single enhancer capable of binding to the promoters of these genes and turning them on. There are, of course, two alleles of the enhancer but only one is active (one is methylated; the other is not). Presumably, when the active enhancer encounters the promoter of an olfactory gene, it turns it on and ceases its search. Thus only one olfactory receptor gene gets to be expressed in a single cell, but which one is a matter of chance.
Now we have a mechanism for discriminating among a thousand or so odorants. However,
- Each receptor is probably capable of binding to several different odorants — some more tightly than others. (The cells described above also responded — although more weakly — to 3 related odorants.)
- Each odorant is capable of binding to several different receptors.
This provides the basis for combinatorial diversity. It would work like this:
- Odorant A binds to receptors on neurons #3, #427, and #886.
- Odorant B binds to receptors on neurons #2, #427, and #743.
The brain then would interpret the two different patterns of impulses as separate odors.
This mechanism appears capable of discriminating between as many as a trillion different mixtures of odorants.