Ch. 6: Communication, Integration & Homeostasis

1. Ch. 6: Communication, Integration & Homeostasis Describe cell to cell communication Explain signal transduction and signal pathways Review homeostasis and its control pathways Goals

2. Cell to Cell Communication 75 trillion cells / 2 types of signals 4 basic methods of cell to cell communication: • Direct cytoplasmic transfer • Contact dependent signals (see IS discussion) • Short distance (local) • Long distance (through combination of signals) Cell receiving signal = ?

3. Gap Junctions for Direct Signal Transfer • Connexins form connexons (channels) • Gate open  cytoplasmic bridges form functional syncytium • Transfer of electrical and chemical signals (ions and small molecules) • Ubiquitous, but particularly in heart and GI tract muscle

4. Local Communication via Paracrines and Autocrines (Chemical signals secreted by cells) Mode of transport ? Examples: Histamine, cytokines, eicosanoids Many act as both

5. Long Distance Communication Body has two control systems: 1) Endocrine system communicates via hormones • Secreted where? Transported where and how? • Only react with ____________ 2) Nervous system uses electrical and chemical signals (APs vs. neurotransmitters and neurohormones) Fig 6-2

6. Cytokines for Local and Long Distance Signaling • Act as paracrines, autocrines or hormones • Difference to “real” hormones (sometimes blurry → e.g. EPO): • Broader target range • Made upon demand (no storage in specialized glands) • Involved in cell development and immune response

7. Signal Pathways • Signal molecule (ligand) • Receptor • Intracellular signal • Target protein • Response

8. 3 Receptor Locations Cytosolic or Nuclear Lipophilic ligand enters cell. Often activates gene. Slower response. Cell membrane Lipophobic ligand cannot enter cell. Outer surface receptor needed. Faster response. Fig 6-4

9. Membrane Receptor Classes • Chemically (ligand) gated channels e.g.: nicotinic Ach receptor • Receptor enzymes • G-protein-coupled Signal transduction

10. Direct Mechanisms via Chemically Gated Channel: Nicotinic ACh receptor Change in ion permeability changes membrane potential

11. Signal Transduction • Activated receptor alters intracellular molecules to create response • First messenger  transducer  amplifier  second messenger Fig 6-8

12. Most Signal Transduction uses G-Protein 100s of G protein-coupled receptor types known G protein is membrane transducer (binds GDP / GTP  name!) Activated G proteins • open ion channels, or • alter intracellular enzyme activity, e.g.: via adenyl cyclase (amplifier)  cAMP (2nd messenger)  protein kinase activation 

13. Activated G-protein Opens Ion Channel Muscarinic ACh receptor

14. Activated G-protein Alters IC Enzyme Activity Epinephrine Signal Transduction Compare to Fig 6-11

15. Novel Signal Molecules: Ca2+ • Important IC signal • Can enter cell via voltage, ligand, and mechanically gated channels • Also intracellular storage • Ca2+ signals lead to various types of events • Movement of contractile proteins • Exocytosis

16. Gases and Lipids as Signal Molecules • NOis made from arginine • short acting auto- and paracrine • in brain and in blood vessels • CO in nervous tissue and smooth muscle • Eicosanoids are arachidonic acid derivatives • Leukotrienes (important in asthma) • Prostanoids (ubiquitous) also important in inflammation etc.

17. Modulation of Signal Pathways Receptors exhibit Saturation, yetReceptors can be up- or down-regulated (grow fewer, grow more) Excess stimulation and drug tolerance Specificity, yet- Multiple ligands for one receptor: Agonists (e.g. nicotine) vs. antagonists (e.g. tamoxifen) - Multiple receptors for one ligand (see Fig 6-18) Competition Aberrations in signal transduction  _____________(table 6-3) Many drugs target signal transduction (SERMs, -blockers etc.)

18. In Summary: Receptors Explain Why Chemicals traveling in bloodstream act only on specific tissues One chemical can have different effects in different tissues

19. Control Pathways: Response and Feedback Loops Cannon's Postulates (concepts) of properties of homeostatic control systems Nervous regulation of internal environment Tonic level of activity → “how much?”, not ON or OFF - regulated by nerve signal frequency Many systems have antagonistic controls (insulin/glucagon) Chemical signals can have different effects on different tissues Failure of homeostasis? Fig 6-20

20. Maintenance of Homeostasis Via local or long distance pathways • Local: autocrines and paracrines • Long-distance: reflex control • Nervous • Endocrine • both

21. Steps of Reflex Control Stimulus Sensory receptor Afferent path Integration center Efferent path Effector (target cell/tissue) Response Fig 6-23

22. Receptors (or Sensors) • Different meanings for “receptor”: sensoryvs. membrane receptors • Can be peripheral or central • Constantly monitor environment • Have threshold (= minimum stimulus necessary to initiate signal) Fig 6-24

23. Afferent Pathway From receptor to integrating center Afferent pathways of nervous system: ? Endocrine system has no afferent pathway (stimulus comes directly into endocrine cell)

24. Integrating Center Receives info about change Interprets multiple inputs and compares them with set-point Determines appropriate response (→ alternative name: control center) Location depends on type of reflex

25. Efferent Pathway From integrating center to effector NS  electrical and chemical signals ES  chemical signals (hormones)

26. Effectors • Cells or tissues carrying out response • Target for NS: _________________________________ • Target for ES: __________________________________

27. Response Loops Begin with Stimulus – End with Response Response takes place at 2 levels • Cellular response of target cell • Opening of a channel • Modification of an enzyme etc... • Systemic response at organismal level • Vasodilation, vasoconstriction • Lowering of blood pressure etc....

28. Feedback Loops Modulate the Response Loop • Response loop is only half of reflex!  Response becomes part of stimulus and feeds back into system. • Purpose: keep system near a set point • 2 types of feedback loops: - feedback loops + feedback loops Fig 6-26 Fig 6-27

29. The Body’s 2 Control Systems • Variation in speed, specificity and duration of action • Compare the different types of reflexes (Table 6-5) • Simple (pure) nervous • Simple (pure) endocrine • Neuro-hormone • Neuro-endocrine (different combos) Fig 6-31

30. Diabetes mellitus the end