Gustatory system

Overview
The gustatory system is the sensory system for the sense of taste.

Importance
Humans require a way to distinguish between safe and dangerous foods. Bitter and sour foods we find unpleasant, while salty, sweet, and meaty tasting foods generally provide a pleasurable sensation. The five specific tastes received by gustatory receptors are salty, sweet, bitter, sour, and umami, which means “savory” or “meaty” in Japanese.

According to Lindemann, both salt and sour taste mechanisms detect, in different ways, the presence of sodium chloride in the mouth. The detection of salt is important to many organisms, but specifically mammals, as it serves a critical role in ion and water homeostasis in the body. It is specifically needed in the mammalian kidney as an osmotically-active compound which facilitates passive re-uptake of water into the blood. Because of this, salt elicits a pleasant response in most humans.

Sour taste can be mildly pleasant in small quantities, as it is linked to the salt flavour, but in larger quantities it becomes more and more unpleasant to taste. This is because the sour taste can signal over-ripe fruit, rotten meat, and other spoiled foods, which can be dangerous to the body because of bacteria which grow in such mediums. As well, sour taste signals acids (H+ ions), which can cause serious tissue damage.

The bitter taste is almost completely unpleasant to humans. This is because many nitrogenous organic molecules which have a pharmacological effect on humans taste bitter. These include caffeine, nicotine, and strychnine, which compose the stimulant in coffee, addictive agent in cigarettes, and active compound in many pesticides, respectively. It is interesting to note that many common medicines have a bitter taste if chewed; this is because most medicines are poisons taken in controlled doses. In this manner, the unpleasant reaction to the bitter taste is a last-line warning system before the compound is ingested and can do damage.

Sweet taste signals the presence of carbohydrates in solution. Since carbohydrates have a very high calorie count (saccharides have many bonds, therefore much energy), they are desirable to the human body, which has evolved to seek out the highest calorie intake foods, as the human body in the distant past has never known when its next meal will occur. They are used as direct energy (sugars) and storage of energy (glycogen). However, there are many non-carbohydrate molecules that trigger a sweet response, leading to the development of many artificial sweeteners, including saccharin, sucralose, and aspartame. This probably does not mean that this particular taste receiver has very ambiguous criteria, or is “easily fooled”, but rather that our understanding of the system and its evolutionary significance is still fledgling.

The umami taste, which signals the presence of the amino acid L-glutamate, triggers a pleasurable response and thus encourages the intake of peptides and proteins. The amino acids in proteins are used in the body to build muscles and organs, transport molecules (hemoglobin), antibodies, and the organic catalysts known as enzymes. These are all critical molecules, and as such it is important to have a steady supply of amino acids, hence the pleasurable response to their presence in the mouth.

Function
In the human body a stimulus refers to a form of energy which elicits a physiological or psychological action or response. Sensory receptors are the structures in the body which change the stimulus from one form of energy to another. This can mean changing the presence of a chemical, sound wave, source of heat, or touch to the skin into an electrical “action potential” which can be understood by the brain, the body’s control center. Sensory receptors are modified ends of sensory neurons; modified to deal with specific types of stimulus, thus there are many different types of sensory receptors in the body. The neuron is the primary component of the nervous system, which transmits messages from sensory receptors all over the body.

The Neuron
A typical neuron has all the parts an ordinary cell would have, as well as a few which set it apart. The main part of the cell is known as the soma or cell body, which contains the nucleus. Spreading out from the soma are a number of arms known as dendrites, where the neuron receives its message from. A long arm known as the axon connects the soma to a large number of extensions at the other end of the cell, longer axons are covered with fatty cells called Schwann cells, which together form the myelin sheath. Axons with a myelin sheath send nerve message faster, as the action potential can jump from space to space between the Schwann cells (the spaces are known as nodes of Ranvier), increasing the speed. On the end of each extension is an endplate; this is where the neuron connects to the dendrites of other neurons to pass on its message. In between the endplate of one neuron and the dendrite of another is a small empty (mostly) area known as the synapse.

Action Potential
Sensory receptors like those on the tongue change chemical signals into a moving electrical “potential”, which then travels through the nervous system (through many neurons) to the brain. When a stimulus is detected, the response is triggered and the “resting” potential changes to the action potential. While in resting potential, pumps in the neuron walls are constantly actively transporting 3Na+ ions out of the cell for every 2K+ ions that are pumped into the cell; this is accomplished by a structure known as a sodium-potassium pump. At the same time, an open ion gate is allowing K+ ions to flow down the concentration gradient back out of the neuron, while the ion gate for Na+ ions is closed. Thus, more positive ions are leaving the cell than entering, and the inside of the cell has a negative charge (-70mV). When an action potential is triggered, Na+ ions start to enter the cell through a separate gate, increasing the charge in the cell. This in turn triggers the voltage regulated Na+ and K+ channels in the cell wall to change shape. This opens the Na+ channel and closes the K+ channel. Sodium ions rush down the concentration gradient into the cell, but potassium ions are unable to escape, thus the potential in the cell rises to 40 mV. This potential in the cell causes other voltage regulated gates further down the cell to open, and the potential travels as a wave through the neuron, and into the next in the chain. After the potential has passed, the cell enters into a refractory period, to revert the potential to resting potential. To travel from one neuron to the next, the action potential must pass through the synapse. As the action potential travels down the axon, it triggers voltage regulated gates which allow Ca2+ ions to flow into the neuron. From this point there are several different routes which can be taken. Sometimes, these ions cause two or more free-floating chemicals within the cell to bond and form a secondary messenger known as a neurotransmitter. This neurotransmitter is then released from the cell into the synapse through exocytosis, when the vesicle (a small bubble containing the neurotransmitter) they are in merges with the pre-synaptic membrane. The neurotransmitter then goes on to trigger the opening of Na+ ion channels in the post-synaptic membrane, which allows Na+ ions to flow into the dendrite of the next neuron, continuing the action potential. Once the potential has been “passed on”, a different chemical causes the re-uptake of the neurotransmitter, breaking it down and returning it to the pre-synaptic neuron. Some neurotransmitters are acetylcholine, dopamine, serotonin, and GABA. The vesicle system of neurotransmitter release through exocytosis and return to pick up more neurotransmitter is known as the vesicle cycle and it involves, specifically, targeting, tethering, docking, release, membrane recovery and transmitter breakdown and vesicle recycling.

Taste as a form of Chemoreception
Taste is a form of chemoreception which occurs in specialized receptors in the mouth. These receptors are known as taste cells, and they are contained in bundles called taste buds, which are contained in raised areas known as papillae that are found across the tongue. To date, there are five different types of taste receptors known: salt, sweet, sour, bitter, and umami. Each receptor has a different manner of sensory transduction: that is, detecting the presence of a certain compound and starting an action potential which ultimately alerts the brain. It is a matter of debate whether each taste cell is tuned to one specific tastant or to several; Smith and Margolskee claim that “gustatory neurons typically respond to more than one kind of stimulus, [a]lthough each neuron responds most strongly to one tastant” (35). Researchers believe that the brain interprets complex tastes by examining patterns from a large set of neuron responses. This enables the body to make “keep or spit out” decisions when there is more that one tastant present. “No single neuron type alone is capable of discriminating among stimuli or different qualities, because a given cell can respond the same way to disparate stimuli” (39). As well, serotonin is thought to act as an intermediary hormone which communicates with taste cells within a taste bud, mediating the signals being sent to the brain. With that in mind, specific types of taste receptors will now be discussed. Receptor molecules are found on the apical (on top) microvilli of the taste cells.

Salt
Arguably the simplest receptor found in the mouth is the salt (NaCl) receptor. An ion channel in the taste cell wall allows Na+ ions to enter the cell. This on its own depolarizes the cell, and opens voltage-regulated Ca2+ gates, flooding the cell with ions and leading to neurotransmitter release. This sodium channel is known as EnAC and is composed of three subunits. EnAC can be blocked by the drug amiloride in many mammals, especially rats. The sensitivity of the salt taste to amiloride in humans, however, is much less pronounced, leading to conjecture that there may be additional receptor proteins besides EnAC that may not have been discovered yet.

Sour
Sour taste signals the presence of acidic compounds (H+ ions in solution). There are three different receptor proteins at work in sour taste. The first is a simple ion channel which allows hydrogen ions to flow directly into the cell. The protein for this is EnAC, the same protein involved in the distinction of salt taste (this implies a relationship between salt and sour receptors and could explain why salty taste is reduced when a sour taste is present). There are also H+ gated channels present. The first is a K+ channel, which ordinarily allows K+ ions to escape from the cell. H+ ions block these, trapping the potassium ions inside the cell (this receptor is classified as MDEG1 of the EnAC/Deg Family). A third protein opens to Na+ ions when a hydrogen ion attaches to it, allowing the sodium ions to flow down the concentration gradient into the cell. The influx of ions leads to the opening of a voltage regulated Ca2+ gate. These receptors work together and lead to depolarization of the cell and neurotransmitter release.

Bitter
There are many different classes of bitter compounds which can be chemically very different. It is interesting that the human body has evolved a very sophisticated sense for bitter substances: we can distinguish between the many radically different compounds which produce a generally “bitter” response. This may be because the sense of bitter taste is so important to survival, as ingesting a bitter compound may lead to injury or death. Bitter compounds act through structures in the taste cell walls called G-protein coupled receptors (GPCR’s). Recently, a new group of GPCR’s was discovered, known as the T2R’s, which it is thought respond to only bitter stimuli. When the bitter compound activates the GPCR, it in turn releases gustducin, the G-protein it was coupled to. Gustducin is made of three subunits. When it is activated by the GPCR, its subunits break apart and activate phosphodiesterase, a nearby enzyme, which in turn converts a precursor within the cell into a secondary messenger, which closes potassium ion channels. As well, this secondary messenger can stimulate the endoplasmic reticulum to release Ca2+, which contributes to depolarization. This leads to a build-up of potassium ions in the cell, depolarization, and neurotransmitter release. It is also possible for some bitter tastants to interact directly with the G-protein, because of a structural similarity to the relevant GPCR.

Sweet
Like bitter tastes, sweet taste transduction involves GPCR’s. The specific mechanism depends on the specific molecule. “Natural” sweeteners such as saccharides activate the GPCR, which releases gustducin. The gustducin then activates the molecule adenylate cyclase, which is already inside the cell. This molecule increases concentration of the molecule cAMP, or adenosine 3', 5'-cyclic monophosphate. This protein will either directly or indirectly close potassium ion channels, leading to depolarization and neurotransmitter release. Synthetic sweeteners such as saccharin activate different GPCR’s, initiating a similar process of protein transitions, starting with the protein Kinase A(PKA), which ultimately leads to the blocking of potassium ion channels.

Umami (Savory)
It is thought that umami receptors act much the same way as bitter and sweet receptors (they involve GPCR’s), but not much is known about their specific function. It is thought that the amino acid L-glutamate bonds to a type of GPCR known as a metabotropic glutamate receptor (mGluR4). This causes the G-protein complex to activate a secondary receptor, which ultimately leads to neurotransmitter release. The intermediate steps are not known.

Transmission to Brain
In humans, the sense of taste is conveyed via three of the twelve cranial nerves. The facial nerve (VII) carries taste sensations from the anterior two thirds of the tongue, the glossopharyngeal nerve (IX) carries taste sensations from the posterior one third of the tongue while a branch of the vagus nerve (X) carries some taste sensations from the back of the oral cavity.