II Sensory Chemoreceptors: A diverse and evolutionarily ancient class of receptors.

II Sensory

Chemoreceptors: A diverse and evolutionarily ancient class of

receptors

Olfactory Receptor Neurons and the Olfactory Epithelium

The olfactory system is designed to detect volatile chemicals present in the air

• Airborne chemicals reach the olfactory epithelium from the external air (or from volatile components released as food is consumed).

• The pathway followed by olfactory neuron axons crosses the cribiform plate and enters the brain: this is one path into a highly protected zone…

Primary olfactory neurons can regenerate

• the neurons turn over with a half-life of 1-2 months.

• Exposure to chemicals can lead to olfactory neuron death – for example, zinc salts can be used to eliminate them experimentally.

• Accidents that accelerate or decelerate the brain relative to the skull can sever the axons of olfactory neurons as they exit the cribriform plate, leading to a temporary anosmia.

Olfactory neurons

and support

cells and the

neuron’s membrane

features that allow integration and action potential

generation.

Illustration of how the graded

receptor potential is transformed into spikes where the decrementally

conducted signal exceeded

threshold and active channels

are present. In the axon, there are

only spikes seen traveling to the

CNS.

Airborne or aerial chemical detection requires special features:• The mucus (illustrated 2 slides back) is both

watery and viscous. Mucus protects the sensitive cilia of the receptor neurons from drying, but it also does something much more crucial in the transduction process…

• The chemicals that we can smell are typically hydrophobic – so the problem of dissolving in the watery mucus has to be solved. The next slide has information relevant to this process.

In the secreted mucus there are odorant-

binding proteins:

beta barrels -->

• Odorant-binding proteins are secreted (by Bowman’s glands) in the olfactory mucus of all land vertebrates. The basic structure of these diverse proteins (there may be over 2,000) is that of a beta barrel; two barrels unite to form the functional dimer, which holds an odorant molecule inside.

Electrical responses

to chemicals indicate that the

receptors for

odorants are

present on the cilia

Nature of the olfactory receptorsNote: these are distinct from the odorant binding molecules

• 1. 7 transmembrane-spanning regions coupled to G proteins.

• 2. Large gene family devoted to these receptor proteins – 1000 genes in dogs and mice, 400 in the human genome.

• Each receptor neuron expresses only one of the receptor genes; all the cells with the same odorant sensitivity project to the same postsynaptic cells in the olfactory bulb. This is the first step in neural coding of odorants.

The “labeled-line” organization of

olfactory receptors: first revealed by exposing a rat to the pure odor of green bell pepper! (All the receptors could be

shown to have the receptor for that odor and they all could be traced to the same glomerulus in the olfactory bulb.)

The olfactory transduction cascades – Yes, there are 2…

• 1. Adenyl cyclase pathway: G protein activation leads to activation of adenyl cyclase. Cyclic AMP opens cation channels admitting Na+ and Ca++. The Ca++ then opens a Cl- channel that further depolarizes the cell.

• 2. IP3 pathway: The activated G protein activates phospholipase C which generates IP3; the IP3 opens cation (Na+ and Ca++) channels and Ca++ opens Cl- channels.

The adenyl cyclase pathway: part 1

Adenyl cyclase, second stage…Golf stands for the olfactory form of the G protein in olfactory cells

The IP3 Pathway

Second messenger families: some examples of odors that evoke them

Switching Modalities: Taste

Taste = Gustation

Taste cells: modified epithelial cells

• Cells regularly wear out and are replaced by division of stem cells (basal cells).

• There are at least the following tastes: sweet, sour, bitter, salty, umami, metallic (?) -- and therefore taste cells possess multiple transduction mechanisms.

• More than 90% of the cells respond to two “tastants”, and many respond to all…

• There is a lot of diversity in taste competence among the vertebrates

Ordinary epithelial channels (ENaC) are used by both salt and hydrogen ions, and H+ can block K+ channels

Sweet receptors can be tricked by a wide variety of molecules that are not similar to glucose…

Bitter has multiple transduction mechanisms

PDE is phospho-diesterase; gustducin got its name before we realized that it is just a g-protein.

Umami reception is for amino acids, such as “Accent” (monosodium glutamate)

Taste transduction has mainly been studied in animals like catfish and rats…

• Many differences exist in the taste capabilities and mechanisms of different vertebrates – for instance, rats can taste pure water – whether or not the information is relevant to human gustation is unclear.

Gustation issues relevant to human biology and health

• The chemosensory senses decline with age, posing problems for elderly people with regard to the palatability of food and the ability to detect food spoilage.

• There are significant genetic differences between individual human subjects in ability to taste bitter molecules – due to the fact that there are 3 families of receptor proteins. These differences significantly affect food choice.