Sensory Systems Notes
Senses provide information to the body about external stimuli. The biochemical machines and systems you have learned to date provide you with the tools for understanding the five senses - smell, taste, vision, hearing, and taste.
The sense of smell involves the detection in the air of relatively small molecules. When it comes to the detection of these molecules, their shapes are more important than their physical characteristics. Many humans are unable to detect specific smells, a condition called anosmias. These deficiencies are often inherited. Olfaction (the sense of smell) arises from the ability of the main olfactory epithelium to detect volatile odoroants. Over one million sensory neurons are found in this region. 7TM receptors, GTP, G proteins, and cAMP all play roles in olfaction. Olfactory receptors (ORs) are responsible for providing the sense of smell. Over 500 such receptors are present in humans, with over 1000 in mouse and rat. The OR gene family is one of the largest gene families in humans. More than half of the human OR genes, however are not functional. By contrast, virtually all rodent OR genes are functional, suggesting that the sense of smell has become less important for survival of higher organisms.
OR proteins are somewhat similar in sequence (20%) to the beta-adrenergic receptor and to each other (30-60%). Each olfactory neuron expresses (synthesizes) only a single OR gene. Binding of an odorant to an OR initiates a signal transduction cascade that results in an action potential in the associated nerve cell. Binding of an odorant to its receptor activates a G protein (called Golf) that activates adenylates kinase, which synthesizes cAMP, which binds to a cation channel protein that allows calcium and other cations to enter the cell. The neuronal membrane is thus depolarized, and initiates and action potential that is propagated, leading ultimately to recognition of the 'smell'. How is the 'sense' of smell derived? First, almost every odorant activates more than one receptor. Second, almost every receptor is activated by more than one odorant. Smells, as such, then correspond to the 'blends' of receptors that are activated at any given time. Importantly, neurons that express specific ORs are linked to specific sites in the brain. Thus, the brain can then 'poll' the various regions of itself to determine what 'smell' is being detected.
The sense of taste (gustation) is related to the sense of smell. They do, however, differ in several ways. Some compounds can be tasted, but not smelled, such as salt and sugar. Though thousands of smells can be detected, only five primary tastes can be discerned. They include bitter, sweet, sour, salty, and umami (glutamate). Molecules that can be tasted are called tastants. Protons are the simplest tastant and they are perceived as sour. Many bitter compounds are alkaloids or related compounds that are toxic. Numerous compounds, including carbohydrates, simple peptides, and some proteins are perceived as sweet. Tastants are perceived by specialized structures called taste buds. Taste buds contain about 150 cells with microvilli projections that are rich in taste receptors. Sensory neurons are important components of taste buds and they carry electrical impulses to the brain as they detect stimulants. A G protein alpha subunit called gustducin is expressed primarily in taste buds.
7TM receptors are involved in detection of bitter and sweet tastes. Approximately 50-100 7TM receptors involved in taste are found in the human genome. One such bitter receptor is called T2R-1. The compound cycloheximide stimulates the T2R-1 equivalent (called mT2R-5) to cause gustducin to bind GTP. Mice with mutations in mT2R-5 do not respond to cycloheximide. Each taste receptor expresses many different members of the T2R family of receptors, in contrast to the olfactory system, which expresses one receptor typer per cell. As a consequence, our ability to detect more smells than tastes occurs because odorants stimulate unique patterns of neurons, whereas many tastants stimulate the same neurones.
The ability to sense 'sweet' compounds also is rooted in 7TM receptors. Simultaneous expression of two members of the 7TM sweet receptor family are required for cells to be able to respond to sweet compounds. Salty tastants, by contrast, are not detected by 7TM receptors. Instead, they are detected by passage directly through ion channels on the surface of the tongue. One class of these channels is sensitive to amiloride. This compound obscures the taste of salt and lowers neuron activity relating to sodium. The amiloride-sensitive sodium channel has a pore covered by cysteine-rich regions of a transmembrane protein.
The last taste sense is the ability to taste the amino acid glutamate. The taste is called umami and is distinct from the other tastes. One class of glutamate receptors is a 7TM receptor with a large amino terminal domain projecting out of the membrane. This domain of the protein appears to be involved in binding glutamate. One glutamate receptor gene called mGluR4, which is a protein expressed as a glutamate receptor (neurotransmitter) in brain, as well as on the tongue. The mRNA for the tongue gene lacks a region of the brain mRNA for the same gene that involves the highest glutamate binding sensitivity. Thus, the tongue protein is not as sensitive for binding glutamate as the same protein made in brain.
Vision is made possible by photoreceptor cells called rod and cones, based on their shapes. Cones function in bright light and give color vision. Rods function in dim light and do not recognize color. Human retinas have about 100 million rods and 3 million cones. Rods can recognize a single photon. The photoreceptor in rods is a protein linked to 11-cis retinal. This complex is called rhodopsin. The protein component of it is called opsin. Opsin is a 7TM receptor. Retinal is connected to opsin by a Schiff base linkage between the epsilon amino group of a lysine (#296) in opson and the aldehyde end of retinal. Rhodopsin absorbs light strongly in the visible region.
Isomerization (due to light energy) of the double bond at position 11 of retinal between the cis and trans forms causes a signal to be produced that gives rise to the detection of light. This happens because the isomerization physically moves the nitrogen atom of the Schiff base of rhodopsin about 5 Angstroms, creating the all-trans form of retinal. The movement leads to the closing of ion channels and the generation of a nerve pulse. Note that transducin is a G protein associated with rhodopsin. Its activation (binding GTP) causes release of the beta and gamma units, as other G protein complexes. The remaining alpha G protein is a cGMP phosphodiesterase. Cleavage of cGMP to GMP causes cGMP to be released from the cGMP-gated ion channel, which in turn causes the channel to close. As a result, the membrane hyperpolarizes and a nerve signal is generated. The process is reversed by hydrolysis of GTP to GDP by the alpha subunit, reassocation of the beta and gamma subunits. In addition, the enzyme guanylate cyclase acts to resynthesize cGMP from GTP. Calcium plays an important role by inhibiting guanylate cyclase. This entire process occurs rapidly, allowing humans to perceive continuous motion at about 1000 frames per second.
Color vision arises from three distinct photoreceptor proteins in cone cells with absorption maxima of 426, 530, and 560 nm. By contrast the absorption maximum of rhodopsin of rod cells is about 500 nm. The sequence of each of the cone photoreceptor proteins is approximately 40% identical with that of rhodopsin. The blue photoreceptor is about 40% identical with the red and green photoreceptors and the red and green photoreceptors are more than 95% identical to each other. Red and green photoreceptors are obviously close to each other evolutionarily. This is born out by biology. Dogs and mice that diverged from primates do not have red photoreceptors and do not sense that end of the spectrum well. Bird sense the spectrum quite well, due to have six photoreceptors, but their red receptor is not evolutionarily related to our red photoreceptor.
Color blindness in humans arises due to the sequence relationships between the red and green photoreceptor pigments. The genes for these two proteins both lie on the X chromosome. Related sequences can frequently undergo genetic recombination, resulting in loss of a photoreceptor and an inability to discriminate a particular color well.
Hearing and touch are related in that they rely on mechanical stimuli. Our hears detect sound with frequencies of 200 to 23,000 cycles per second (Hertz). Our ears are capable of hearing sound sources delayed by only 0.02ms, allowing us to distinguish between the time it takes for sound to travel to each of our ears. Consequently, we are able to pinpoint the direction a sound emanates from fairly precisely.
Sound waves are detected in the cochlea of the inner ear. The primary detection is by hair cells. Cochlea contain about 16,000 hair cells and each hair cell contains a bundle of 20-300 hairlike projections called sterocilia. Mechanical movement of a hair bundle by sound waves generates a nerve potential. This appears to occur as a result of connections between stereocilia called tip links. Slight movements cause tip links to 'pull' open or 'push' closed openings to ion channels, generating the signal for nerve transmission.
The detection of pressure and the detection of temperature are two essential elements of the sense of touch. Amiloride-sensitive sodium channels like those in taste are important. Other systems detect high temperature, acid, or specific chemicals.
The sense of touch is linked to the ability to sense pain. Nociceptors are specialized neurons that transmit signals to the spine and brain when tissue is damaged, creating the pain sensation. Capsaicin, the 'hot' component of spicy foods interestingly activates nociceptors. Note that a pore region of the receptor is identified and this is thought to allow calcium to flow into the cell when the receptor binds capsaicin. The receptor is exquisitely sensitive to capsaicin and also responds to heat, and dilute acid. Thus, VR1 responds to several damaging stimuli. Mice deficient in VR1 are not affected by food containing high amounts of capsaicin and are not very sensitive to heat. Birds, which consume peppers containing capsaicin do not appear to be sensitive to it either.