1. Abstract
Sensory
receptors are transducers that convert a physical signal in the outside world
into a cellular signal that can be integrated, transmitted, processed and
interpreted by the nervous system. While the assortment of different types of
sensory receptor is able to detect and selectively respond to a wide range of
diverse extracellular signals they all work in basically the same way according
to common blue print. They are compartmentalized input-output cells. For a
specific signal to be detected it must first act on specialized membrane
proteins (detector proteins) in the input or transduction region of the cell.
This interaction generates a change in membrane voltage (receptor potential) by
opening or closing ion channels either directly or indirectly via an enzyme
cascade that controls the concentration of an intracellular second messenger (a
cyclic nucleotide or calcium). The resulting electrical signal is communicated
to the output region of the cell where it regulates Ca2+dependent exocytosis of a chemical transmitter
that carries the sensory signal to the next cell in the sensory pathway. These
are the basic steps that underlie the operation of all sensory receptors. While
the identity of the individual components will vary from one receptor type to
another, the general blue print by which they function remains the same.
1. Introduction
Our goal here is to cover the basic features of sensory receptors to gain a general understanding of how they work. Why should we care how they work? Imagine you were born without any of your senses, no sight, hearing, smell, taste, touch, no sense of balance, gravity, hot, nor cold; no sensory input what so ever, nothing, and you were kept alive by whatever means necessary for 21 years at which time the question is would you have a thought in your head? If so what could it possibly be about, where could it have come from, what could have provoked it? This is a famous question first posed by David Hume, an 18th century Scottish philosopher, who used it to support the empirical conclusion that everything we know including our concept of self is derived from our sensory receptors [1]. If this is not enough to arouse an interest in how sensory receptors work, consider what your sex life would be like without them.
2. Sensory receptors are classic input / output devices
The input is a signal from the outside world, where the outside world includes both the external world that we live in as well as the internal world that the cells we are made of live in. While our sensory receptors can selectively detect tens of thousands of different external and internal signals there are only four different types or modalities of stimuli: chemical (chemoreceptors), mechanical (mechanoreceptors), light (photoreceptors) and temperature (thermoreceptors). The output of the sensory receptor is a chemical transmitter that is released by Ca2+dependent exocytosis of transmitter containing vesicles using the same sequence of events that control the release of neurotransmitter at a synapse.
Sensory receptors are polarized cells with spatially segregated input and output compartments. The input or transduction compartment communicates with the output or synaptic terminal of the receptor cell via a change in membrane potential, a receptor potential that is generated by an increase or decrease in current flow into the cell through an ion channel (Figure 1). So, to understand how sensory receptors work we need to understand how the input signal operates (gates) an ion channel.
The surface membrane of the input compartment is populated by membrane proteins, which we will refer to as detector proteins. They are designed in such a way that the protein undergoes a conformation change when it receives a specific signal. This could be the binding of a ligand in the case of some, but not all, chemoreceptors, the application of a mechanical force (tension, shear, pressure, torque) in the case mechanoreceptors, electromagnetic radiation in the case of photoreceptors and heat in the case of thermoreceptors. The conformational change that is triggered by arrival of the sensory signal either directly gates (opens or closes) an ion channel that is an integral part of the detector protein, making the detector a receptor ion channel complex, or the conformational change activates a detector protein that is G Protein Coupled Receptor (GPRC), which in turn excites a G protein coupled enzyme cascade that ultimately gates an ion channel via change in the concentration of an intracellular second messenger, typically a cyclic nucleotide (cGMP of cAMP)or Ca2+ (Figure 2). In all known cases the ion channel that is controlled by the detector protein is a non-selective cation channel with a reversal potential typically near 0 mV. This results in a receptor potential that is either depolarizing (stimulus opens channel) or hyperpolarizing (stimulus closes channel). In all but two types of sensory receptors the transduction process generates a depolarizing receptor potential. The two exceptions, in which the receptor potential is hyperpolarizing are vertebrate photoreceptors, where the light activation of visual pigment (a GPRC) stimulates the hydrolysis of cGMP causing a cyclic nucleotide-gated cation channel in the surface membrane to close and certain types mechanoreceptors in which a decrease in force can cause the closure of mechanosensitive cation channels that are open under resting conditions
Sensory receptors that use a detector protein ion channel complex to convert a physical stimulus into an electrical signal include many kinds of chemoreceptors, taste receptors for salts and acids, all types of mechanoreceptors and thermoreceptors [2-14]. Stimuli that are transduced by GPRC detector proteins include photoreceptors, olfactory receptors, taste receptors for sweet, bitter and umami tastants and a host of receptors for signaling molecules used in cell-to-cell communication, such as hormones [15-18].
The receptor
potential is a local voltage change generated in the transduction region of the
receptor with an amplitude that depends on the strength of the sensory
stimulus, i.e. the number of detector proteins affected by the stimulus and
thus the number of gated ion channels. The local receptor potential reaches the
synaptic region of receptor cell via either passive spread or a conducted
action potential depending on the distance between the input and output regions
of the cell (Figure 3). Local voltage changes
get smaller and slower as they spread passively from their site of generation,
a consequence of what is commonly referred to as the cable properties of the
cell [19].If
the receptor cell is compact and the distance separating the transduction and
synaptic regions is short the decrement of the receptor potential is small and
does not interfere with the transfer of information from the input to the
output regions of the cell. These receptors are commonly referred to as primary
sensory receptors (they do not generate action potentials)
examples, include retinal rods and cones, auditory and vestibular hair cells
and taste receptor cells. If the distance between the transduction and synaptic
regions of the cell is too large for effective communication via passive
spread, as in the case of olfactory receptors as well as cutaneous touch and
temperature receptors, the expression of voltage gated Na+channels in the intervening axon region of the cell
support the generation of action potentials allowing the sensory information contained ina depolarizing
receptor potential to be conducted to the synaptic terminal via a single or
train of action potentials depending on the amplitude of the receptor
potential (Figure 3).
3. Conclusion
Sensory
receptors generate an electrical signal in response to a diverse assortment of
stimuli delivered in the form of either chemical, mechanical, radiant (light)
or heat energy. In all cases they couple sensory input to synaptic output via a
similar sequence of events (a common blue print) that follows a course based on
three defining characteristics: 1. detector protein is either an ion channel
complex or GRPC. 2. Receptor potential either depolarizing (the most common
case) or hyperpolarizing. 3. Input (transduction) region of the cell
communicates with the output (synaptic) region of cell via either passive electrical
spread (primary sensory receptors) or conducted action potentials.
Figure
1:
Sensory Receptors are compartmentalized input / output cells. The input is a
physical stimulus that is detected by specialized membrane proteins in the
transduction region of the cell. This generates a receptor potential (see Figure 2) that is communicated to the synaptic region
where it triggers a change in the output (synaptic release) of a chemical
transmitter (see Figure 3).
Figure
2:
The transduction of a physical stimulus into an electrical signal is mediated
by detector proteins that are either a detector ion channel complex or a G
Protein Coupled Receptor (GPRC). Ion channels that are an integral part of the detector
protein complex are cation selective and gated directly by the direct action of
the physical stimuli they are designed to detect, which could be force, in case
of mechanoreceptors, ligand binding, in the case of some types of
chemoreceptors or heat, in the case of thermoreceptors. Detector proteins that
are G Protein Coupled Receptors (GPRCs) are activated by either light, in the
case of photoreceptors, of ligand binding in the case olfaction, some types of
taste receptors and signal molecules used for cell-to-cell communication. The
activated GPRC turns on a G protein coupled enzyme cascade that changes the
level of an intracellular second messenger
that gates a cation selective ion channel producing
eithera depolarizing or hyperpolarizing
receptor potential depending on whether the second messenger level increased or
decreased.
Figure 3: Receptor potentials reach the synaptic region of sensory
receptors cell either by passive spread in compact cells without an axon or by triggering
a propagated action potential in receptors that express voltage gated Na+ channels and have an axon. In both cases the
electrical signal that reaches the synaptic region of the cell influences
voltage-gated Ca2+channels to either
increase (if sensory signal is depolarizing) or decrease (if sensory signal is
hyperpolarizing) Ca2+-dependent
exocytosis of chemical transmitter.
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