Physiology

• The study of cell communication focuses on how a cell gives and receives messages with its environment and with itself
• Cells do not live in isolation. Their survival depends on receiving and processing information from the outside environment
• Cells have developed complex mechanisms of communication so that they can receive a message, transfer the information across the plasma membrane, and then produce changes within the cell in response to the message

  
• Intracellular signaling


  Communication within a cell in response to internal and external stimuli

  
• Intercellular signaling


  Cell interacts with other cells of the body (cell signaling)
• Direct Intercellular Communication


  • Cells exchange chemicals through connections between the cytoplasm (gap junctions, transient direct linkup of surface markers)
• Indirect Intercellular Communication through Chemical Messengers

  • The messenger must bind to a matching receptor and stimulate a response

  
• Cells typically communicate using chemical signals or chemical messengers called ligands
• In order to detect a signal, a neighbor cell (that is to be a target cell) must have the right receptor for that signal

  
• When a signaling molecule (or ligand) binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell

  
• The original intercellular (between-cells) signal is converted into an intracellular (within-cell) signal that triggers a response

  
• Cell Signaling


  1. Reception: a signaling molecule or ligand binds to a receptor protein in the membrane

  2. Transduction: passing on the signal (can occur in one step, but is usually a sequence of changes in a series of "relay molecules")

  3. Response: cellular changes due to the signal

  
• Categories of chemical signaling

  • Autocrine signaling
  • Paracrine signaling
  • Endocrine signaling
  • Direct signaling across gap junctions

  
• Autocrine signaling


  A cell responds to its own signaling molecule

  
• Paracrine signaling


  Signals that act locally between cells that are close together

  
• Endocrine signaling


  Signals from distant cells, originating from endocrine cells

  
• Direct signaling


  Transfer of ions or small molecules from one cell to its neighbor through pores in the membrane (gap junctions)
• Receptors


  Protein molecules in the target cell or on its surface that bind to ligands
• Types of receptors


  • Plasma membrane receptors (cell surface receptors)
  • Intracellular receptors

  
• Plasma membrane receptors


  • Transmembrane proteins that span the entire membrane thickness, with hydrophobic segments within the membrane, hydrophilic segments extending out from the membrane into the extracellular fluid, and other hydrophilic segments extending into the intracellular fluid

  
• Intracellular receptors


  • Not located in membranes but exist in either the cytosol or the cell nucleus, respond to hydrophobic ligand molecules that can travel across the plasma membrane, have a segment that binds the chemical messenger (ligand) and other segments that act as regulatory sites, and have a segment that binds to DNA

  
• Features defining receptor-ligand interactions

  • Specificity
  • Affinity
  • Saturation
  • Competition
• Specificity


  The ability of a receptor to bind only one type or a limited number of structurally related types of chemical messengers

  
• Only cells that express the correct receptor can bind a particular messenger

  
• The receptor functions as a molecular switch that elicits the cell's response when "switched on" by the messenger binding to it

  
• Affinity


  The strength with which a chemical messenger binds to its receptor
• Norepinephrine causes muscle cells of the heart to contract faster

  But, via the same type of receptor, regulates certain aspects of behavior by acting on neurons in the brain
• Receptor


  Functions as a molecular switch that elicits the cell's response when "switched on" by the messenger binding to it

  
• Acetylcholine


  • Excitatory at the neuromuscular junction in skeletal muscle, causing the muscle to contract
  • Inhibitory in the heart, where it slows heart rate
• These opposite effects are possible because two different types of acetylcholine receptor proteins are found in the two locations
• The degree to which a particular messenger binds to its receptor is determined by the affinity of the receptor for the messenger

  
• High-affinity binding sites


  Binding sites that tightly bind a ligand
• Low-affinity binding sites


  Binding sites that weakly bind the ligand
• A receptor with high affinity will bind at lower concentrations of a messenger than will a receptor of low affinity
• Differences in affinity of receptors for their ligands have important implications for the use of therapeutic drugs in treating illness; receptors with high affinity for a ligand require much less of the ligand (that is, a lower dose) to become activated
• Chemical specificity


  Depends on the shape of the binding site of the receptor
• Affinity


  Depends on the strength of the attraction between the protein (receptor) and the ligand
• Different proteins/receptors may be able to bind the same ligand: in these cases, these receptors have the same chemical specificity for the ligand but have different affinities for that ligand
• The closer the surfaces of the ligand and binding site are to each other, the stronger the attractions
• The more closely the ligand shape matches the binding site shape, the greater the affinity