Cell Physiology - Fall 2024 Lecture Notes PDF

Cell Physiology Dr. Andrei B. Belousov (405) 271-8001, ext. 32064 [email protected] 1 What will be on CELL PHYSIOLOGY and ANS exams? What about alternative sources? You: “An article on internet says something different from what yo...

Cell Physiology Dr. Andrei B. Belousov (405) 271-8001, ext. 32064 [email protected] 1 What will be on CELL PHYSIOLOGY and ANS exams? What about alternative sources? You: “An article on internet says something different from what you told us” Besides, this is a basic science. Do not be surprised if you hear something different from what is in my lectures 2  Cell Physiology Overview Basic cell functions Ø passive and active solute transport, osmolarity, tonicity, principles of cell communication - Lectures 1 & 2 Specialized functions: Ø electrophysiology - Lectures 3-6 Ø muscle physiology - Lectures 7 & 8 3 Passive Solute Transport 1) You do not spend energy 2) You go only where they move you Cell physiology Fall 2024: Cell physiology lecture lecture 1 1 4  Learning Objectives 1. Describe negative feedback, positive feedback and feed forward systems. 2. List intracellular and extracellular concentrations of Na+, K+, Ca++ and Cl-. 3. List functions of membranes. 4. List characteristics of passive transport systems. 5. List variables that affect diffusion of solutes across membranes and know how changes in those variables affect diffusion of solutes. 6. List which types of solutes can cross the membrane by simple diffusion and what types of solutes require transport system to pass across membranes. 7. List the types of channels and describe their characteristics. 8. List the characteristics of carrier proteins. 9. List characteristics of facilitated diffusion. 10. Describe the difference between transport by simple diffusion and transport by carrier proteins. 5 Homeostasis and Passive Solute Transport Outline 1. Homeostasis and Feedback Systems 2. Composition of Body Fluids 3. Membrane Structure and Function 4. Passive Transport - Simple diffusion - Pores - Channels - Carrier proteins ∙ Facilitated diffusion 6  Homeostasis and Passive Solute Transport Outline 1. Homeostasis and Feedback Systems 2. Composition of Body Fluids 3. Membrane Structure and Function 4. Passive Transport - Simple diffusion - Pores - Channels - Carrier proteins ∙ Facilitated diffusion 7 HOMEOSTATIC MECHANISMS What is homeostasis? Homeostasis is the process of the maintenance of the composition of the extracellular fluid This is a dynamic process with continuous adjustments being made to maintain the variables in a range that is required for life 8  Each body system has a role in the overall homeostasis of the organism Digestive system Respiratory Renal system system Cardiovascular system Nervous and endocrine systems: regulate these body systems 9 Feedback systems How do we achieve homeostasis? A. Negative feedback B. Positive feedback C. Feedforward 10  What is Negative feedback? A. Negative feedback - maintains homeostasis by opposing deviations of a system from its desired level (“A” increases “B”, then “B” decreases “A”) - this returns a system to the normal values Examples: temperature blood pressure O2 CO2 ion balance, etc. 11 Components of a Negative Feedback System Set Point (desired value) Efferent Pathway (motor) Integrator Effector Controlled variable Sensor Afferent Pathway (sensory) 12  Example: Control of body temperature Negative Feedback - moves the variable in the opposite direction of the change Reference Point: 37oC Efferent Pathway Sweating (-) Brain Body (hypothalamus) temperature Shivering (+) Temperature sensors Afferent Pathway 13 What is Positive Feedback? B. Positive feedback - reinforces movement further away from the set point (“A” increases “B”, then “B” increases “A”) Examples: depolarization phase of an action potential labor shock 14  Example: Positive feedback system to increase Na+ conductance during action potential (this concept will be explained in detail in lecture 4) Vm = -60 mV 15 What is Feedforward? C. Feedforward - is a response in anticipation of a change in a variable Examples: secretion of fluids and digestive enzymes in the GI tract when smelling and/or seeing the food 16  Homeostasis and Passive Solute Transport Outline 1. Homeostasis and Feedback Systems 2. Composition of Body Fluids 3 Membrane Structure and Function 4. Passive Transport - Simple diffusion - Pores - Channels - Carrier proteins ∙ Facilitated diffusion 17 Composition of Body Fluids Total Body Water = 42 liters (for a 70 kg individual) ~60% body weight Intracellular fluid – within cells (25 L) Extracellular Fluid – outside of cells (17 L) (i) Interstitial Fluid (ii) Blood plasma (3 L) – between cells in body tissues (14 L) Blood (5.5 L) includes n intracellular fluid (inside cells) – 2.5 L n extracellular fluid (plasma) – 3 L 18  Composition of Extracellular and Intracellular Fluids (Extracellular) Solute Intracellular Interstitial Plasma conc (mM) conc (mM) conc (mM) Na+ 15 145 145 K+ 150 5 4 Ca2+ 0.0001 1 (free) 2.5 (free) Cl- 7 110 103 19 Composition of Extracellular and Intracellular Fluids (Extracellular) Solute Intracellular Interstitial Plasma conc (mM) conc (mM) conc (mM) Mg2+ 12 1.5 1.5 - HCO3 10 24 21-28 Pi 40 2 1 - 1.5 Amino 8 2 2.3 acids Glucose 1 5.6 5.7 (75-105 mg/dl) (during fasting) ATP 4 0 trace Protein 4 0.2 2.5 (5.5 - 8.0 g/dl) pH 7.2 7.4 7.38 - 7.44 20  Homeostasis and Passive Solute Transport Outline 1. Homeostasis and Feedback Systems 2. Composition of Body Fluids 3. Membrane Structure and Function 4. Passive Transport - Simple diffusion - Pores - Channels - Carrier proteins ∙ Facilitated diffusion 21 As you could see, there is difference in the concentration of solutes between the intracellular and extracellular fluids What creates and maintains this difference? Membranes! 22  Membrane Structure and Function Nucleus Plasma membrane Secretory vesicles Golgi apparatus Endoplasmic reticulum Mitochondria 23 Membranes are a bilayer of lipids (6-10 nm thick) with proteins imbedded in the bilayer 6-10 nm 24  Two major types of membrane lipids a. Phospholipids Glycerol Two fatty acid chains (non-polar, hydrophobic; “phobic” in Latin “fear”) Polar phosphate group (forms hydrophilic head; “philic” - in Latin “attraction”) b. Cholesterol ? Do you need to know chemical structure? 25 Phospholipids and cholesterol Create hydrogen bonds with other polar molecules and face the surface of the membrane Oriented away from water molecules forming the inner core of the bilayer Cholesterol - associates with the phospholipids to reduce the fluidity of the membrane 26  Membranes also contain proteins hydrophobic interactions with fatty acids hydrogen bonds Also, if a protein (either transmembrane or peripheral) is permanently attached to the biological membrane, it is called an integral protein (e.g., nACh receptors in the end-plate) 27 Functions of membranes Regulate passage of substances into and out of the cell (forming selective barrier) Detect chemical messengers arriving at cell surface (through receptors) Recognition of “self” (immune function) Link cells to the extracellular matrix (forming tissues) Link adjacent cells together by membrane junctions (regulation of solute transport; role in cell-to-cell communication) 28  Membrane junctions are specialized structures between cells Tight Junctions Gap Junctions 29 Tight Junctions – structures that encircle cells and join adjacent cells 30  Tight Junctions – form barrier between cells and control (or prevent) the movement of solutes between cells Tight junctions are characterized by “leakiness” - this is whether they pass or do not pass water The “leakiness” varies among tissues X Paracellular pathway 31 Gap Junctions – large channels between cells These channels allow small molecules and ions to pass between cells They are important for the synchronized contraction of smooth and cardiac muscle cells 32  Transport of solutes across the plasma membrane -Passive -Active 33 Homeostasis and Passive Solute Transport Outline 1. Homeostasis and Feedback Systems 2. Composition of Body Fluids 3. Membrane Structure and Function 4. Passive Transport - Simple diffusion - Pores - Channels - Carrier proteins ∙ Facilitated diffusion 34  Passive solute transport across membranes does not require external energy solutes travel down their concentration or electrochemical gradients 35 After concentrations across Solutes diffuse across the lipid bilayer by the membrane become equal, the NET movement across the simple diffusion membrane becomes “0” A B A B Brownian motion Solutes in solutions constantly move because of the Brownian motion The NET movement of solutes is in a direction from high concentration to low concentration The NET movement continues until solute concentrations across the membrane in compartments “A” and “B” become equal - Simple diffusion - Pores - Channels After that, the molecules still move, but the NET movement is “0” - Carrier proteins * Facilitated diffusion 36  What determines the rate of diffusion across membranes? Diffusion equation: J = PA (Co-Ci) J = net flux A = surface area of membrane Co-Ci = concentration difference across membrane P = permeability coefficient (the ability of the solute to pass through the lipid bilayer) Hydrophobic solutes (non-polar molecules) have high permeability coefficients and diffuse rapidly through the lipid bilayer Hydrophilic solutes (ionized and polar - Simple diffusion molecules) have low permeability coefficients - Pores - Channels and diffuse slowly through the lipid bilayer - Carrier proteins * Facilitated diffusion 37 Solutes that are soluble in lipids have a high membrane permeability O2 CO2 N2 - Simple diffusion - Pores - Channels Gases - Carrier proteins * Facilitated diffusion 38  Solutes that are soluble in lipids have a high membrane permeability Fatty acids Steroids Ethanol Cholesterol - Simple diffusion Lipophilic - - Pores Channels molecules - Carrier proteins * Facilitated diffusion 39 Large polar molecules (e.g., glucose) and large charged molecules (e.g., AA) do not diffuse across the lipid bilayer Polar molecules are those with uneven distribution of charge (e.g., glucose) - charges are different at each end glucose Charged molecules are those that have either “+” or “-” charge (e.g., AA) glutamate - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 40  Water does not easily diffuse across the lipid bilayer (For comparison: action potential may pass 3.7 miles per 1 min) Water molecule also is polar, but it is very small It can diffuse, but VERY 6-10 nm slowly (1 min) - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 41 Ions do not Na+ diffuse across the lipid bilayer K+ Ca2+ Cl- - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 42  However, normal cell functioning REQUIRES transport of large polar molecules, large charged molecules and ions across the membrane There are several transport systems that help with transport of such solutes 43 Passive transport via membrane proteins: PORES Pores are transmembrane proteins in membranes that provide a passage for solutes across the membrane Always open Passage is in both directions, but always down the solute’s concentration gradient Example: passage of water through aquaporins Aquaporins - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 44  Passive transport via membrane proteins: ION CHANNELS Channels are transmembrane proteins that + allow passage of ions across the membrane (including Na+, K+, Ca2+ and Cl-) Normally they are closed (there are exceptions, e.g., “leak” channels that are always open) The opening of a channel is called “gating” There are channels that are bidirectional, some channels permit ions to flow only in one direction, but the ions always pass via channels by diffusion down their electrochemical gradient “Gate” - - Simple diffusion Pores - Channels - Carrier proteins * Facilitated diffusion 45 Types of ion channels a. Ligand-gated channels b. Voltage-gated channels c. Mechanically-gated channels (mechano-receptors) - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 46  Voltage-gated Ligand-gated channels Mechanically-gated channels channels Voltage - + sensor Ligand- binding receptor - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 47 Selectivity for ions a. Size of ion b. Charge of ion - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 48  Passive transport via membrane proteins: CARRIER PROTEINS Carriers are transmembrane proteins that allow passage of molecules (e.g., glucose, urea, etc.) The transport is passive: it does not require energy Molecules are transported down their concentration gradient Transport occurs in both directions Carriers work in cycles (carriers are also used for active transport, but this is the subject of the next lecture) - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 49 X X X X X X X X X X X X X X Extracellular Example: glucose or urea Intracellular X X - Simple diffusion - Pores Passive transport via membrane - Channels - Carrier proteins proteins: CARRIER PROTEINS (down concentration gradient) * Facilitated diffusion 50  Carrier protein characteristics 1. Specificity. Carrier requires a specific structure and charge of solutes These “shapes” do not fit this transporter and will not be transported by this carrier, e.g., glucose vs. amino acid - - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 51 Carrier protein characteristics 2. Competition. Molecules of similar structure compete for this transporter for example glucose, galactose and fructose compete with each other to be transported by GLUT2 transporter - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 52  Carrier protein characteristics 3. Saturation. Transport will plateau when all of the transporters are occupied Solute Carrier protein Tm (the maximal transport) - Simple diffusion - Pores - Channels - Carrier proteins Solute concentration * Facilitated diffusion 53 Simple diffusion does not saturate with increasing the concentration of solute, but the diffusion via carriers does For example, O2 but also water molecules (via aquaporins) For example, glucose - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 54  Facilitated diffusion (also known as “mediated transport”) Most often this term is used for passive transport of molecules via carriers (e.g., glucose, urea, etc.) o The transport is passive: it does not require energy o Molecules are transported down their concentration gradient o Transport occurs in both directions However, more generally this term is used for passive transport of any solutes via transport proteins o facilitated diffusion of water via aquaporins (down concentration gradient) o facilitated diffusion of ions via ion channels - Simple diffusion (down electrochemical gradient) - - Pores Channels - Carrier proteins * Facilitated diffusion 55 Facilitated diffusion (also known as “mediated transport”) For this course: Facilitated diffusion is passive transport of molecules via CARRIER PROTEINS (e.g., glucose, urea, etc.) and not passive transport via pores or ion channels - Simple diffusion - Pores - Channels - Carrier proteins * Facilitated diffusion 56  Summary of Pores, Channels and Carriers Pores Channels Carriers (e.g., aquaporin) (e.g., K+ channel) (e.g., Glut2 glucose transporter) conduction always transiently transporter through open open cycles membrane translocation 2 x 109 106-108 200-50,000 rate (max) particles/sec particles/sec particles/sec (fastest transport) (slowest transport) The transporters that work in cycles are slow and can saturate This includes the primary and secondary active transporters (next lecture) 57