1. POWERPOINT ® LECTURE SLIDE PRESENTATION by LYNN CIALDELLA, MA, MBA, The University of Texas at Austin Additional material added by J Padilla for Physiology 31 at ECC Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings HUMAN PHYSIOLOGY AN INTEGRATED APPROACH FOURTH EDITION DEE UNGLAUB SILVERTHORN UNIT 1 PART A 6 Communication, Integration, and Homeostasis

2. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Cell-to-Cell Communication: Overview  Physiological signals  Electrical signals  Changes in cell’s membrane potential  Chemical signals  Secreted by cells into ECF  Responsible for most communication within the body  Target cells, or targets, receive signals  Four basic methods of communication  Gap junctions- direct transfer from cell to cell  Contact-dependent signals- ligand bound to cell attaches to receptor  Local Communication- autocrine and paracrine signals  Long-distance communication- nerve impulses and hormones

3. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Cell-to-Cell Communication: Methods Direct contact and local cell-to-cell communication Gap junctions transfer both chemical and electrical signals found in any cell type, they are the only means of direct electrical signal transfer CAMs transfer signals in both directions- CAMS= cell adhesion molecules linked to cytoskeleton and intracellular enzymes Figure 6-1a

4. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-1c Cell-to-Cell Communication: Methods Paracrine and autocrine are chemical signals- use interstitial fluid to travel to adjacent cells but do not go a long distance

5. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-2a Cell-to-Cell Communication: Methods Long distance cell-to-cell communication

6. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-2b Cell-to-Cell Communication: Methods Neurotransmitters have a rapid effect Neuromodulators act as paracrine or autocrine signals and have a slower effect. All cells are exposed to hormones and neurohormones but only target cells respond to them.

7. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-4 (1 of 2) Signal Pathways: Receptor locations Target cell receptors- Located in any area of the cell. Lipophilic signals(mostly hormones) bind intracellularly. Lipophobic singals stay in the ECF and bind receptor proteins.

8. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings The chemical properties of a ligand predict its binding site: Hydrophobic/lipid-soluble: cytosolic or nuclear receptors, typically change gene expression, leading to slow but sustained responses examples: steroid hormones, thyroid hormones Hydrophilic/lipid-insoluble: membrane-spanning receptors typically activate rapid, short-lived responses that can be of drastic impact. examples: epinephrine, insulin,… Control of Cells by Chemical Messengers How hormones and other signals work Communication requires: signals (ligands) and receptors (binding proteins).

9. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 5-1 Epinephrine b i n d s h e r e … cellular response begins … Receptors on the surface of a cell are typically proteins that span the membrane.

10. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 5-2 Cells B & C lack the matching receptors for this chemical messenger, so they are not directly affected by the signal. Only Cell A has the matching receptors for this chemical messenger, so it is the only one that responds.

11. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

12. Figure 6-3 Signal Pathways: Overview

13. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-5 Signal Pathways: Membrane Receptors Four categories of membrane receptors

14. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-7 Signal Pathways: Signal Amplification Transducers convert extracellular signals into intracellular messages which create a response

15. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-8 Signal Pathway: Biological Signal Transduction

16. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-9 Signal Pathway: Signal Transduction Steps of a cascade Steps of signal transduction pathway form a cascade

17. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-10 Signal Pathway: Receptor Enzymes Tyrosine kinase, an example of receptor-enzyme Ligands include growth factors, cytokines, insulin.

18. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Signal Pathway: GPCR- G protein coupled receptors  Membrane-spanning proteins -  Cytoplasmic tail linked to G protein, a three-part transducer molecule – changes from GDP to GTP to become activated  When G proteins are activated, they -  Open ion channels in the membrane -  Alter enzyme activity on the cytoplasmic side of the membrane – they link to amplifier enzymes

19. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-11 GPCR: Adenylyl Cyclase-cAMP ******** The G-protein coupled adenylyl cyclase- cAMP system G-protein receptors are the most abundant type One signal molecule Adenylyl cyclase ATP cAMP G protein Protein kinase A Phosphorylated protein Cell response G protein- coupled receptor Signal molecule binds to G protein-linked receptor, which activates the G protein. Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response. G protein turns on adenylyl cyclase, an amplifier enzyme. Adenylyl cyclase converts ATP to cyclic AMP. cAMP activates protein kinase A. 1 2 3 4 5 1 2 3 4 5

20. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-12 GPCR: The Phospholipase C System ********* Ca 2+ Membrane phospholipid PL-C IP 3 PK-C Protein + P i Cell membrane Extracellular fluid Intracellular fluid DAG Phosphorylated protein KEY PL-C=phospholipase C DAG=diacylglycerol PK-C=protein kinase C IP 3 =inositol trisphosphate ER=endoplasmic reticulum ER Receptor G protein Cellular response Signal molecule Signal molecule activates receptor and associated G protein. G protein activates phospholipase C (PL-C), an amplifier enzyme. PL-C converts membrane phospholipids into diacylglycerol (DAG), which remains in the membrane, and IP 3, which diffuses into the cytoplasm. DAG activates protein kinase C (PK-C), which phosphorylates proteins. IP 3 causes release of Ca 2+ from organelles, creating a Ca 2+ signal. Ca 2+ stores 1 2 3 4 5 12345 Includes second messengers molecules

21. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-13, step 1 Signal Pathway: Receptor-Channel ********* Extracellular signal molecules Ions Ion channel Receptor-channels open or close in response to signal molecule binding. 1 1 Gated channels control the flow of ions and influence the concentration gradient contributing to changes in membrane potential.

22. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-13, steps 1–2 Signal Pathway: Receptor-Channel Extracellular signal molecules Ions Ion channel G protein G protein- coupled receptor Receptor-channels open or close in response to signal molecule binding. Some channels are directly linked to G proteins. 1 2 1 2

23. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-13, steps 1–3 Signal Pathway: Receptor-Channel Extracellular signal molecules Ions Ion channel G protein G protein- coupled receptor Intracellular signal molecules Receptor-channels open or close in response to signal molecule binding. Some channels are directly linked to G proteins. Other ligand-gated channels respond to intracellular second messenger. 1 2 3 1 2 3 Binds to molecules dissolved in the ECF, or to G- protiens, or to second messenge rs.

24. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-13 Signal Pathway: Receptor-Channel Extracellular signal molecules Ions Ion channel G protein Change in membrane permeability to Na +, K +, Cl – Creates electrical signal Voltage-sensitive protein Cellular response G protein- coupled receptor Intracellular signal molecules Receptor-channels open or close in response to signal molecule binding. Some channels are directly linked to G proteins. Other ligand-gated channels respond to intracellular second messenger. 1 2 3 1 2 3 Found in areas where quick changes are necessary like in nervous and muscle

25. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-14 Signal Pathway: Signal Transduction Summary map of signal transduction systems

26. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-15 Novel Signal Molecules: Calcium*********  Calcium as an intracellular messenger:  Most versatile ion; enters ICF through gated channels  Stored in the ER or moved in by active transport Rapid increases of Ca2+ in the ICF triggers other chemical reaction cascades initiated by binding proteins Extracellular fluid Intracellular fluid Electrical signal Ca 2+ released from intracellular Ca 2+ stores Ca 2+ Ca 2+ binds to proteins Ca 2+ Calmodulin Other Ca 2+ -binding proteins Alters protein activity ExocytosisMovement Chemical signal Ca 2+ in cytosol increases. Voltage-gated Ca 2+ channel opens.

27. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-20 Control Systems: Tonic Control Physiological control systems keep regulated variables within a desired range during homeostasis Tonic control of blood vessel diameter

28. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Control Systems: Cannon’s Postulates  Nervous regulation of internal environment – maintain conditions that allow normal function  Tonic control – continous monitoring that changes a condition with increased or decreased signaling- primarily done by NS  Antagonistic control – NS or endocrine send separate signals for increasing or decreasing a response  One chemical signal can have different effects in different tissues – the effect is based on the type of receptor the molecule binds

29. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-21a Control Systems: Antagonistic Control

30. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-22 Control Pathways Comparison of local and reflex control Steps in a reflex control pathway – two alternate routes Integrating centers determine whether the incoming signal is within setpoint range

31. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-24 Control Pathways: Receptors Multiple meanings of the word receptor

32. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-25 Control Pathways: Response Loop Thermometer Wire Water temperature increases to 30˚ C Heater Wire to heater Water temperature is 25˚ C STIMULUS SENSOR or RECEPTOR AFFERENT PATHWAY INTEGRATING CENTER EFFERENT PATHWAY TARGET OR EFFECTOR RESPONSE Water temperature is below the setpoint. Thermometer senses temperature decrease. Signal passes through wire to heater. Water temperature increases. Heater turns on. Signal passes from sensor to control box through the wire. Control box is programmed to respond to temperature below 29 degrees. Reflex steps Control box 1 2 3 4 5 6 7 1 2 3 4 5 6 7 A nonbiological response loop

33. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-26 Control Pathways: Setpoints Oscillation around the setpoint -  Acclimatization refers to natural adaptation – natural conditions  Acclimation refers to induced adaptation – often in a lab setting

34. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-27a Control Pathways: Feedback Loops Negative and positive feedback Feedforward control refers to anticipatory responses Negative feedback maintains homeostasis by opposing or removing the signal but cannot prevent an initial stimulus

35. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-27b Control Pathways: Feedback Loops

36. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-29a Control Pathways: Setpoints Circadian rhythms Pre-set homeostatic changes based on environmental conditions- helps to predict and prepare for changes.

37. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Control Systems: Speed and Specificity PropertyNeuralEndocrine SpecificitySingle targetMost cells Nature of signalElectrical  chemical Chemical SpeedRapidSlower DurationVery shortLonger Coding for stimulus intensity Intensity = frequency Intensity = amount of hormone

38. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-31 Control Pathways: Review Some basic patterns of neural, endocrine, and neuro- endocrine control pathways Stimulus T Simple neural reflex Receptor Afferent neuron CNS integrating center Efferent neuron Neuro- transmitter Target cell Response T Stimulus Neurohormone reflex Blood vessel Response Stimulus E T Endocrine integrating center Response Stimulus E Endocrine cells Neurohormone Neurotransmitter RRR E1E1 E2E2 R T R Stimulus Response Hormone #2 Response T Stimulus E R Response T Hormone R E S Stimulus Endocrine cell Receptor(sensor) Sensory neuron (afferent pathway) CNS or endocrine integrating center T Neurotransmitter Neurohormone Classic hormone Efferent neuron Target cell (effector) Efferent pathways KEY Neuroendocrine reflexes Simple endocrine reflex 123456