Session 2: The role of receptors and receptor potentials in intercellular communication

Question 1

Define a physiological ligand and a physiological receptor.

Answer 1

Physiological ligand: A physiological substance that “binds to”/interacts with a receptor, and which may be a neurotransmitter, a hormone, a local mediator and even an antibody.

Physiological receptor: Cell components (proteins) or modified sensory neurons that discriminate and sometimes also help to convert environmental information into a form that can be interpreted by the cell.

Question 2

Make a distinction between sensory and cell component/ cell-specific (cell membrane-associated and intracellular) receptors.

Answer 2

Sensory receptors:
modified sensory neurons or a part thereof/ a specialised cell that can convert environmental disturbances or internal physiological change( stimulus) into a graded electrical signal( called a receptor potential), which when it reaches or exceeds a particular threshold potential, initiates an action potential in the associated sensory fiber.

Cell component/ cell-specific (cell membrane associated and intracellular) receptors:
specific 3D plasmalemma or intracellular proteins

Question 3

Discuss the functional role of physiological receptors (sensory and cell-specific receptors) in the human body.

Answer 3

They discriminate and convert sensory signals into neural signals that the organism uses to survive and maintain homeostasis.

Question 4

Explain the concept “signal transduction”.

Answer 4

Definition: the process of converting a sensory, neural, or ligand- mediated message into an action potential or an activated signaling pathway in a sensory receptor or cell specific receptor bearing target cell (which produces a sensory or biochemical response)

• The sensory stimulus produces a graded receptor potential in the sensory receptor. This graded receptor potential will trigger an action potential in the associated nerve axon, if the threshold potential is reached.

Question 5

Classify cell-surface receptors into five clinically important principal categories according to their mechanisms of action.

Answer 5

1. Ligand-gated ion channels
2. Membrane-bound tyrosine kinase receptors
   insulin receptors
3. Serine-kinase receptors
4. G-protein coupled receptors
5. Cytokine receptors

Question 6

Give an example of a ligand-gated ion receptor.

Answer 6

Nicotinic cholinergic receptor

Question 7

Discuss the membrane-bound tyrosine kinase receptor.

Answer 7

• An example is the insulin receptor
• Undergo autophosphorylation after ligand-binding
• Contain the effector system as an intrinsic part of their
  structure
• Contains an enzymatic activity within an intracellular
  domain that phosphorylates tyrosine residue
• When the hormone is bound, the tyrosine kinase is
  stimulated to autophosphorylate tyrosine residues on
  the receptor, which phosphorylates other proteins
  within the cell

Question 8

Discuss G-protein coupled receptors.

Answer 8

• Where a G protein alpha sub-unit is activated and
  mediates signal transduction through various enzymes
  such as adenylate cyclase or phospholipase C.
• When activated, these membrane receptors initiate
  the release of other intracellular events via GTP-
  binding proteins.
• The nucleotide-regulating proteins (G proteins), bind
  guanine nucleotides and provide great diversity for
  coupling to different receptors.

Question 9

Discuss the serine-kinase receptors.

Answer 9

Serine is an amino acid.

Question 10

Discuss the cytokine receptors.

Answer 10

• Growth hormones and prolactin bind here
• Ligand-binding induces receptor binding to
  intracellular kinases which catalyses protein
  phosphorylation

Question 11

Make a distinction between membrane-associated and intracellular receptors and identify examples of ligands that exert their physiological effects by binding to these receptors.

Answer 11

Check table.

Question 12

Identify factors that determine whether a ligand is going to elicit a cell response.

Answer 12

1. Receptor specificity
2. Receptive field
3. Receptor affinity, reaction rate and equilibrium

Question 13

Explain the concepts “ligand-receptor reaction rate”.

Answer 13

How quickly a ligand binds and dissociates from its receptor.

Question 14

Explain “ligand-receptor equilibrium”.

Answer 14

A steady state that is reached when the ligand binds and dissociates at the same rate.

Question 15

Explain “receptor affinity”.

Answer 15

Differences in concentrations of hormones between free and receptor-bound forms, the difference between binding and dissociation rates and the equilibrium constants which reflects the affinity for the hormone/ligand for its receptor.

Question 16

Define and explain the concept “receptor adaptation” as applied to cell component receptors, and state different mechanisms by which it occurs.

Answer 16

A change in the sensitivity (and subsequent frequency of nerve impulse generation) in many sensory and some cell-component receptors after a period of time in the presence of a constant stimulus.

Question 17

Briefly describe three clinically important subtypes of cell surface receptor-mediated signaling.

Answer 17

1. Ligand-gated ion channel receptors: open a specific
   ion channel
2. Surface receptors with protein kinase domains:
   phosphorylate protein substrates inside the cell
3. G-protein associated cell surface receptors: cause
   intracellular changes via second messengers.

Question 18

Explain the concepts serpentine receptors, autoreceptors, and death domain receptors.

Answer 18

Serpentine receptors (G-protein coupled receptors):
receptors which span cell membranes seven times in a snake-like fashion. 

Autoreceptors:
Receptors which are located in the cell membrane of presynaptic nerve cells.

Death domain receptors:
Receptors which cause programmed cell death (apoptosis).

Question 19

Distinguish 5 main classes of sensory receptors according to the agent that stimulates them and and the sensory stimuli they detect. Identify at least two stimuli for each main class.

Answer 19

1. Mechanoreceptors
   - touch, position, hearing, equilibrium, arterial pressure
2. Thermoreceptors
   - heat and cold
3. Nociceptors
   - pain
4. Electromagnetic receptors
   - vision, e.g. rods
5. Chemoreceptors
   - taste, smell, arterial O2, osmolality, blood
   glucose/amino acids/fatty acids.

Question 20

Briefly describe the 4 steps of a typical signal transduction cascade.

Answer 20

1. A stimulus arrives at a sensory receptor
   - usually sodium ion channels open in the sensory receptor membrane, allowing current to flow usually inward, which produces depolarisation of the receptor.
2. Increased sodium ion entry:
   - depolarises the membrane to produce a decremental,
   non-propagating receptor potential.
3. If the sensory receptor potential reaches or exceeds the threshold, an action potential is generated at the sensory neuron.
4. Initiation of action potentials occurs at the first node of Ranvier (or adjacent electrically excitable membrane in unmyelinated axons).

Question 21

Briefly describe sensory receptor adaptation.

Answer 21

• Receptor adaptation may result from receptor
  structure readjustment or an electrical type of
  accommodation in the terminal fiber.
• Prolonged exposure to ligands causes most receptors
  to become unresponsive (desensitised). There are 2
  types of desensitisation:
• homologous desensitisation - receptor loses
  responsiveness to one specific ligand
• heterologous desensitisation - receptor loses
  responsiveness to multiple ligands
• Mechanism of receptor adaptation depends on
  receptor type:
  1. Slow adapting receptors: continue responding to a
  prolonged stimulus
  2. Rapid adapting receptors: show a more rapid
  decrease in action potential frequency with time, in
  response to a prolonged stimulus.

Question 22

Distinguish between temporal and spatial summation in sensory nerve receptors.

Answer 22

Spatial summation: increasing numbers of fibers carry signals simultaneously to another neuron.

Temporal summation: repeated sequential action potentials in one presynaptic neuron.

Question 23

Define a receptor potential.

Answer 23

A graded membrane potential generated when a sensory receptor has discriminated a sensory stimulus and which can generate an action potential, if the threshold potential of the membrane is reached.

Question 24

Briefly describe the ionic events involved in the generation of sensory receptor potentials.

Answer 24

• During rest, membranes are polarised
• The membranes of receptor endings of afferent nerve
  fibers are very excitable and respond to a particular
  form of energy.
• Excitability indicates possibility of changes in
  membrane permeability for one or another type of ion.
• Stimulation usually increases Na+ membrane
  permeability with a gradual increase in Na+ influx
• Because Na+ ions are positively charged, this leads to
  a gradual decrease in membrane potential and the
  membrane becomes less polarised (hypodepolarised)
• This hypodepolarisation is called the receptor potential.

Question 25

Compare the ways in which the nervous and endocrine systems convey messages in the human body.

Answer 25

Nervous system:
Electrical signals are transferred by neurons that deliver chemical messages with rapid and precise localisation. Generally, these messages need to be repeated after a short time and only cells with direct neural innervation via synapses can receive messages.

Endocrine system:
Hormones are secreted into the bloodstream and spread throughout the body. Time course over which a message is transmitted, performs its function and is terminated in the endocrine system is much slower than in the nervous system and doesn’t need to be repeated as often.

Question 26

Briefly explain why knowledge of sensory and cell component receptors is clinically important.

Answer 26

• Therapeutic and toxic effects of drugs usually result
  from their interaction with protein macromolecules
• Drug receptors are macromolecules
• The molecular size, shape and electrical charge of a
  drug determine whether and which affinity a drug will
  bind to a particular receptor
• Many drugs change the functioning of a
  macromolecule (act as an agonist)

Question 27

Briefly explain why knowledge of sensory and cell component receptors is clinically important.

Answer 27

• Therapeutic and toxic effects of drugs usually result
  from their interaction with protein macromolecules
• Drug receptors are macromolecules
• The molecular size, shape and electrical charge of a
  drug determine whether and which affinity a drug will
  bind to a particular receptor
• Many drugs change the functioning of a
  macromolecule (act as an agonist)
  -True pharmalogical antagonists interact with receptors
  w/o altering the receptor’s functioning , i.e. have no
  intrinsic activity.
• A pure antagonist prevents the binding of an agonist
  and blocks its actions.
• Most drug receptors are proteins
• Therapeutic agents either mimic the

Question 28

Briefly explain why knowledge of sensory and cell component receptors is clinically important.

Answer 28

• Therapeutic and toxic effects of drugs usually result
  from their interaction with protein macromolecules.
• Drug receptors are macromolecules.
• The molecular size, shape and electrical charge of a
  drug determine whether and which affinity a drug will
  bind to a particular receptor.
• Many drugs change the functioning of a
  macromolecule (act as an agonist).
  -True pharmalogical antagonists interact with receptors
  w/o altering the receptor’s functioning , i.e. have no
  intrinsic activity.
• A pure antagonist prevents the binding of an agonist
  and blocks its actions.
• Most drug receptors are proteins.
• Therapeutic agents either mimic the the actions of
  endogenous ligands such as neurotransmitters or
  endocrine hormones or act as receptor antagonists to
  prevent the responses to endogenous chemical
  signals.
• Other classes of drug receptors include enzymes,
  transport proteins or pumps and structural proteins.

Question 29

Define a receptor agonist and antagonist, respectively.

Answer 29

Receptor agonist: an analogue of a ligand that can bind to that ligand’s receptor and induce an action that mimics the cellular effect of the natural ligand.
* has intrinsic activity

Receptor antagonist: an analogue that blocks the ligand action, either by preventing ligand binding or binding but not activating the receptor.
* no intrinsic activity

Question 30

Classify membrane potentials into three broad categories.

Answer 30

1. Graded potentials
2. Resting membrane potentials
3. Action potentials

Question 31

State three specific examples of graded membrane potentials.

Answer 31

1. (Sensory) receptor potentials
2. Postsynaptic potentials
3. (Motor) endplate potentials