Physiology Lecture (3) PDF

Physiology Intercellular connections and communications LECTURE (3) DR. El-Sawy 0  Physiology Intercellular...

Physiology Intercellular connections and communications LECTURE (3) DR. El-Sawy 0  Physiology Intercellular connections and communications Types: Tight junctions Desmosomes Gap junctions (Zonula Occludens) (Zonula Adherens)  Junctions that fasten the cells to one another and to surrounding  At apical borders of tissues and hold cells the cells.  Permit transfer of ions together.  Tie cells together and & other molecules from provide tissues with Notes one cell to another. Hemidesmosome & strength and stability focal adhesion attach cells to their basal laminas DR. El-Sawy 1  Physiology Intercellular connections and communications Tight junctions Gap junctions  Attachments between cells at  Attachments between cells Definition their apical borders. that permit intercellular communications  Present in epithelial cells :  Present in cardiac, smooth 1. Renal proximal tubules. muscles & epithelial cells Site 2. Renal distal tubules.  Rare in neurons. 3. Gall bladder.  Absent in skeletal muscles.  Adjacent cell membranes are  Highly non selective fused at ridges (formed of channels allowing all ions Occludin, Claudin proteins) and macromolecules to pass. projecting from adjacent cells.  Consist of 6 similar subunits (connexins) on each cell. Structure  Each set (connexon) of subunits is arranged to form a common pore.  Are intercellular pathways  In cardiac & smooth muscle : for solutes and water. Provide low resistance  May be : path for the spread of ionic 1. Tight: impermeable to currents. solutes and H2O as in renal  In other cells : Functions distal tubule. Facilitate passage of 2. Leaky: permeable as in metabolites & intercellular renal proximal tubule or signals between cells. gall bladder. DR. El-Sawy 2  Physiology Intercellular connections and communications DR. El-Sawy 3  Physiology Intercellular connections and communications  Cells in a multicellular organism communicate by chemical messengers. In local signaling In long-distance signaling  Cells communicate using local  Cells use chemicals called hormones regulators, messenger molecules. (endocrine).  Travel only short distances  Ability of a cell to respond to a (paracrine) and released from signal depends on whether or not it neighboring cells or nerve supply to has a receptor specific to that signal. the organ (synaptic signaling). DR. El-Sawy 4  Physiology Intercellular connections and communications mechanisms of hormone action : Paracrine Autocrine Juxtacrine  The chemical substance  The chemical substance  The chemical substance diffuses through the act on the same cells interact with specific interstitial space to that produce them. receptor on juxta- affect neighboring posed cells. cells. DR. El-Sawy 5  Physiology Intercellular connections and communications Earl Sutherland (Nobel Prize Laurate at 1971 for discovery of cyclic AMP and hormone action) discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through 3 processes. Processes : 1. Reception. 2. Transduction. 3. Response.  Protein molecules in the target cell or on its surface that bind Definition ligands. 1. Intracellular receptors Types 2. Cell Surface Receptors DR. El-Sawy 6  Physiology Intercellular connections and communications  Proteins found in cytosol (cytoplasmic) or nucleus (nuclear) of Def target cells.  Steroid (cytoplasmic) hormone. Examples  Thyroid (nuclear) hormone.  Small or hydrophobic chemical messengers can readily cross the membrane → activate receptors.  Activated hormone-receptor complex (HRC) → can act as a Mechanism transcription factor which bind to specific region in DNA called hormone response element (HRE) → increase the transcription of specific genes in DNA into specific proteins. DR. El-Sawy 7  Physiology Intercellular connections and communications  Each cell-surface receptor has 3 main components: a) External ligand-binding domain (extracellular domain) b) Membrane-spanning region Structure c) Intracellular domain inside the cell  The size and extent of each of these domains vary widely, depending on the type of receptor 1. Ligand-gated ion channel receptors Types 2. G protein-coupled receptors 3. Enzyme-linked Receptor or tyrosine kinase receptors Note Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane. DR. El-Sawy 8  Physiology Intercellular connections and communications Ligand-Gated Ion Channels G-protein coupled receptors Enzyme Linked Receptors receptors  Ion channel-linked receptors bind  It bind a ligand and activate a  They are cell-surface receptors with a ligand and open a channel membrane protein called G protein intracellular domains that are through the membrane that allows (3 subunits α, β & γ subunits) associated with an enzyme e.g. specific ions to pass through. Insulin receptors.  When the chemical messenger  Example: tyrosine kinase receptor. binds to its receptors → activate  The amino acids that line the inside Tyrosine kinase receptor transfers G-protein and alpha subunit of channel are hydrophilic to allow phosphate groups to tyrosine interacts with either an ion channel for the passage of water or ions. molecules. or an enzyme e.g. adenyl cyclase Signaling molecules bind to the or phospholipase C in cell  When a ligand binds to the extracellular domain of two membrane extracellular region of the channel, nearby tyrosine kinase receptors there is a conformational change  Activation of enzyme → excessive , which then dimerize. in protein’s structure → allows ions production of 2nd messengers Phosphates are then added to as sodium, calcium, magnesium, and inside cells as cAMP (by adenyl tyrosine residues on intra- hydrogen to pass through. cyclase), IP3 and DAG (by cellular domain of receptors → phospholipase C) which produce transmit the signal to the next intracellular response. messenger within the cytoplasm. DR. El-Sawy 9  Physiology Intercellular connections and communications Ligand-gated ion channel receptors Enzyme linked receptors DR. El-Sawy 10  Physiology Intercellular connections and communications G-protein-coupled receptors DR. El-Sawy 11