Textbook Notes (362,796)
Canada (158,054)
Physiology (97)

Ferg - Lecture 1.docx

7 Pages
Unlock Document

Western University
Physiology 3140A
Donglin Bai

Cellular Physiology – Dr. Stephen Ferguson General Principles of Receptor Signalling General Characteristics ­ Purpose of cell signalling (communication) is to permit the development of complex mechanisms so that they can govern behaviour of cells for the overall benefit of the organism ­ Cell signalling contributes to: o Regulation of metabolic processes o Cell growth and differentiation o Cell migration/movement o Cell death o Integration of normal physiological responses Cell Signalling 1. Extracellular signalling molecules o Ligands, first messengers o Produced by the cell to signal to their neighbouring cells and/or to regulate their own function 2. Receptor proteins o Bind the extracellular ligand and transduce the information provided by the signalling molecule to the inside of the cell 3. Intracellular signalling molecules & signalling proteins o Distribute the signal to the appropriate parts of the cell o Intracellular signalling proteins include  Protein kinases  GTP-binding proteins  Adaptors  Phosphatases 4. Target proteins o Activities are altered when the signalling pathway is active o Change the behaviour of the cell Signalling Molecules • Proteins • Lipids • Small peptides • Growth factors • Amino acids • Fatty acid derivatives • Nucleotides • Ions • Steroids • Pheromones • Retinoids • Light and dissolved gasses: NO and CO • Hormones Signalling Molecules are: ­ Secreted o From the signalling cell into the extracellular space ­ Released o By passive diffusion through the plasma membrane ­ Exposed o To the extracellular space but remain tightly bound to the surface of signalling cell Receptors ­ Target cell responds by means of a specific receptor protein o Regardless of the signal ­ Binding of the signalling molecule (first messenger) is the primary event which initiates a response in the target cell Receptor Properties: ­ Specificity o One receptor binds to one ligand ­ Saturability o Ligand binding is limited by the number of receptors expressed on a cell o The max response is related to number of receptors expressed ­ High affinity o Many ligands act at very low concentrations  <10^-8M o Endocrine has a very high affinity whereas synaptic receptors may be a lower affinity Cell Response ­ The way a cell responds to its environment varies o Receptor expression  Set of receptors expressed by the cell will determine its response o Intracellular machinery  Depending on the intracellular machinery available to integrate and interpret the information the cell receives  E.g.: complement of kinases • Ion channels • Phosphatases o Ligand targets  Single ligand can produce different physiological effects on different target cells  Does this by binding to multiple receptors that are coupled to distinct effector pathways or by binding to distinct receptor subtypes o Example: Acetylcholine  Stimulates skeletal muscle contraction • nAChR (ion channel)  Decrease rate and force of contraction of heart muscles, mAChR (G coupled) Classes of Receptors 1. Intracellular Receptors ­ Cytosolic/nuclear (steroid receptors) that bind to hydrophobic ligands ­ Many diverse ligands but have similar mechanism of action leading to the activation and direct regulation of transcription of specific genes 2. Cell Surface Membrane Receptors ­ Large number of different receptors divided into distinct receptor “superfamilies” o GPCR o Enzyme linked receptors o Ligand-gated ion channel receptors ­ Majority of receptors are expressed at the surface of a target cell and are activated upon ligand binding ­ Ligands for these receptors are hydrophilic and are unable to pass across the plasma membrane (or are too large) Subclasses of Cell Surface Receptors ­ Three subclasses of cell surface receptors based upon the transduction mechanisms used: 1. Ion Channel Linked Receptors o Transmitter-gated ion channels o Ligand transiently opens or closes the ion channel formed by the protein to which it binds  Leads to brief changes in ion permeability across the plasma membrane and excitability of the target cell o Multi-pass 4-5 transmembrane proteins  Made up of multiple subunits that exhibit different properties based on the composition of the subunit • nAChR • NMDAR • GA 2. G-Protein Linked Receptors o Agonist activation o Indirectly regulate activity of other plasma membrane-bound target proteins  Either enzymes or ion channels o Interaction between receptor and target protein mediated by G protein o There are seven transmembrane spanning proteins  Make up the largest family of receptor proteins 3. Enzyme Linked Receptors o Binding of ligand to receptor leads to direct activation of a receptor linked enzyme  Can also lead to indirect activation of associated enzymes o Most are heterogeneous single pass transmembrane proteins  Have ligand binding sties at the extracellular domain and catalytic sites at the intracellular domain Multiple Forms of Signalling 1. Contact dependent signalling o Some signalling molecules remain bound to surface of signalling cell  Only activate target cells that come in physical contact with the signalling cell o Important in developmental signalling 2. Paracrine signalling o Secreted signalling molecules that act as local mediators of cell signalling o Only impact target cells in the immediate environment o To be effective, signalling molecules can’t diffuse far from the local environment o Affected by:  Local transport mechanisms that take the molecules back into the cell  Extracellular enzymes  Ligand immobilization due to binding to the extracellular matrix 3. Synaptic signalling o For complex multicellular organisms short range signalling isn’t ideal to coordinate cell behaviour o Specialized cells have evolved to regulate communication between widely separated regions of the organism o There are neurons which extend long processes (axons) that enable the cells to make a range of contacts  From cells that are mm to tens of meters away o When activated by a signal form another cell:  Neurons send an electrical impulse along the axon  Impulse reaches end of axon at specialized nerve terminals  Electrical impulse stimulates the calcium dependent exocytosis of neurotransmitter  Neurotransmitters release their neurotransmitters into the synaptic cleft upon activation  Released neurotransmitter acts on receptors on the cell surface of the next cell in the circuit • Depolarizes o Specialized contacts between the nerve terminal of the signalling cell and the target cell are called chemical synapses  During synapse a signal can be specifically transmitted to target cells over long distances o Electrical impulse travels up to 100 m/s and the released neurotra
More Less

Related notes for Physiology 3140A

Log In


Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.