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

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 = ?
Cell receiving signal is target cell

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
syn·cy·ti·um (sĭn-sĭsh'ē-əm) n., pl. -cy·ti·a (-sĭsh'ē-ə).
A multinucleated mass of cytoplasm that is not separated into individual cells.

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
Chemically gated is also referred to as ligand-gated

10. Direct Mechanisms via Chemically Gated Channel: Nicotinic ACh receptor
Most Raid signal pathways change ion flow through channels
Change in ion permeability changes membrane potential

11. Activated receptor alters intracellular molecules to create response
Signal Transduction
Activated receptor alters intracellular molecules to create response
First messenger  transducer  amplifier  second messenger
To transduce = to lead accros
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
NO is 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, yet Receptors 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
Homeo = similar
Tonic = continuous

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

21. Effector (target cell/tissue)
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”: sensory vs. 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:
__________________________________
Target for NS:
muscles and glands and some adipose tissues
Target for ES:
any cell with proper receptor

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. Homeostasis = Dynamic Equilibrium with Oscillation around Set Point
Fig 6-26

30. Negative and Positive Feedback
Fig 6-27
NOT homeostatic !!
Homeostatic
examples

31. Negative Feedback Example

32. 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

33. Diabetes mellitus
the end