Session 2: The role of receptors and receptor potentials in intercellular communication Flashcards
Define a physiological ligand and a physiological receptor.
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.
Make a distinction between sensory and cell component/ cell-specific (cell membrane-associated and intracellular) receptors.
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
Discuss the functional role of physiological receptors (sensory and cell-specific receptors) in the human body.
They discriminate and convert sensory signals into neural signals that the organism uses to survive and maintain homeostasis.
Explain the concept “signal transduction”.
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.
Classify cell-surface receptors into five clinically important principal categories according to their mechanisms of action.
- Ligand-gated ion channels
- Membrane-bound tyrosine kinase receptors
insulin receptors - Serine-kinase receptors
- G-protein coupled receptors
- Cytokine receptors
Give an example of a ligand-gated ion receptor.
Nicotinic cholinergic receptor
Discuss the membrane-bound tyrosine kinase receptor.
- 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
Discuss G-protein coupled receptors.
- 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.
Discuss the serine-kinase receptors.
Serine is an amino acid.
Discuss the cytokine receptors.
- Growth hormones and prolactin bind here
- Ligand-binding induces receptor binding to
intracellular kinases which catalyses protein
phosphorylation
Make a distinction between membrane-associated and intracellular receptors and identify examples of ligands that exert their physiological effects by binding to these receptors.
Check table.
Identify factors that determine whether a ligand is going to elicit a cell response.
- Receptor specificity
- Receptive field
- Receptor affinity, reaction rate and equilibrium
Explain the concepts “ligand-receptor reaction rate”.
How quickly a ligand binds and dissociates from its receptor.
Explain “ligand-receptor equilibrium”.
A steady state that is reached when the ligand binds and dissociates at the same rate.
Explain “receptor affinity”.
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.
Define and explain the concept “receptor adaptation” as applied to cell component receptors, and state different mechanisms by which it occurs.
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.
Briefly describe three clinically important subtypes of cell surface receptor-mediated signaling.
- Ligand-gated ion channel receptors: open a specific
ion channel - Surface receptors with protein kinase domains:
phosphorylate protein substrates inside the cell - G-protein associated cell surface receptors: cause
intracellular changes via second messengers.
Explain the concepts serpentine receptors, autoreceptors, and death domain receptors.
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).
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.
- Mechanoreceptors
- touch, position, hearing, equilibrium, arterial pressure - Thermoreceptors
- heat and cold - Nociceptors
- pain - Electromagnetic receptors
- vision, e.g. rods - Chemoreceptors
- taste, smell, arterial O2, osmolality, blood
glucose/amino acids/fatty acids.
Briefly describe the 4 steps of a typical signal transduction cascade.
- 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. - Increased sodium ion entry:
- depolarises the membrane to produce a decremental,
non-propagating receptor potential. - If the sensory receptor potential reaches or exceeds the threshold, an action potential is generated at the sensory neuron.
- Initiation of action potentials occurs at the first node of Ranvier (or adjacent electrically excitable membrane in unmyelinated axons).
Briefly describe sensory receptor adaptation.
- 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.
Distinguish between temporal and spatial summation in sensory nerve receptors.
Spatial summation: increasing numbers of fibers carry signals simultaneously to another neuron.
Temporal summation: repeated sequential action potentials in one presynaptic neuron.
Define a receptor potential.
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.
Briefly describe the ionic events involved in the generation of sensory receptor potentials.
- 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.
