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Ch. 6: Communication, Ch. 6: Communication, Integration & HomeostasisIntegration & Homeostasis
Describe cell to cell communication
Electrical or Chemical only
Explain signal transduction
Review homeostasis
Goals
N.B.: Running Problem, Diabetes Mellitus
Cell to Cell CommunicationCell to Cell Communication75 trillion cells (In Scientific Notation??)
4 basic methods of cell to cell communication (p 175):
1. Direct cytoplasmic transfer (Gap Junctions)2. Contact dependant signals (Surface
Molecules)3. Short distance (local diffusion)4. Long distance (through either chemical or
electrical signals)
Cell receiving signal = ? receptors
1. Gap Junctions for 1. Gap Junctions for Direct Signal TransferDirect Signal Transfer
Connexins from each cell form connexon (channel)
Gate open cytoplasmic bridges form functional syncytium
Transfer of electrical and chemical signals (ubiquitous, but particularly in heart muscle and smooth muscle of GI tract)
2. Contact-Dependent 2. Contact-Dependent SignalsSignals
Require cell-cell contact
Surface molecules bind
CAMs – Cell Adhesion Molecules
Bidirectional Communication Possible
3. Short distance (local 3. Short distance (local diffusion)diffusion)
Paracrines and Autocrines (Chemical signals secreted by cells)
Para- = next to
Auto- = self
Mode of transport - diffusion (slow)
Histamine, cytokines, eicosanoids
Many act as both
Autocrine
4. Long Distance Communication
Body has two control systems:
Endocrine system communicates via hormones Secreted where? Transported where and how? Only react with ____________
Nervous system uses electrical (along
the axon) and chemical (at the synapse) signals (APs vs. neurotransmitters and neurohormones)
Fig 6-2
Cytokines for Local and Long Distance Signaling
Act as paracrines, autocrines or hormones
Comparison to hormones (sometimes blurry): Broader target range Made upon demand (like steroids, no
storage in specialized glands) Involved in cell development and
immune response Terminology: A zoo of factors in a jungle of interactions
surrounded by deep morasses of acronyms and bleak deserts of synonyms
Signal PathwaysSignal Pathways
Signal molecule (ligand)
Receptor
Intracellular signal
Target protein
Response
Three ReceptorThree Receptor LocationsLocations
Lipophilic ligand: enters cell and/or
nucleus Often activates gene Slower response
Lipophobic ligand can't enter cell Membrane receptor Fast response
Fig 6-4
Membrane, Cytosolic or Nuclear
Membrane Receptor Membrane Receptor ClassesClasses
1. Ligand - gated channel2. Receptor enzymes3. G-protein-coupled4. Integrin
Direct Mechanisms via Ligand-Direct Mechanisms via Ligand-gated Channel: gated Channel: Nicotinic ACh Nicotinic ACh receptorreceptor
Change in ion permeability changes membrane potential
Signal Transductio
n Activated receptor
alters intracellular molecules to create response
First messenger transducer amplifier second messenger
Fig 6-8
Most Signal Transduction uses Most Signal Transduction uses G-Protein G-Protein
Hundreds of types known
Bind GDP / GTP (name!)
Activated G proteins 1. Open ion channels 2. Alter intracellular enzyme activity, e.g.: via adenyl
cyclase (amplifier) cAMP (2nd messenger) protein kinase activation phosphorylated protein
G-Protein is a membrane-associated protein that binds to GDP
G - Protein mediated Signal Transduction
Muscarinic ACh receptor
Epinephrine Signal Transduction
Compare to fig 6-11
Other signal MoleculesOther signal Molecules Not all are proteins Ca2+ is a common cytosolic messenger NO (nitric oxide) is a neurotransmitter Lipids:
Leukotrienes cause contraction of bronchiolar smooth muscle
Prostanoids have several communicative roles, e.g., inflammation
Modulation of Signal Pathways
Receptors exhibit
Saturation, yetReceptors can be up- or down-regulated (e.g. 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 causes many diseases (table 6-3)
Many drugs target signal transduction pathway (SERMs, -blockers etc.)
In Summary: In Summary: Receptors Explain WhyReceptors Explain Why
Chemicals traveling in bloodstream act only on specific tissues
One chemical can have different effects in different tissues
Homeostasis and Homeostasis and “Homeodynamics”“Homeodynamics”
Cannon's Postulates (concepts) of properties of homeostatic control systems
1. Nervous regulation of internal environment
2. Tonic level of activity
3. Antagonistic controls (insulin/glucagon)
4. Chemical signals can have different effects on different tissues
Failure of homeostasis?
Fig 6-19
Tonic Control
Control Pathways: Response and Feedback
LoopsMaintain homeostasisMaintain homeostasis
Local – paracrines and Local – paracrines and autocrinesautocrines
Long-distance Long-distance - - reflex controlreflex control Nervous Nervous EndocrineEndocrine CytokinesCytokines
Steps of ReflexSteps of ReflexControlControl
Steps of ReflexSteps of ReflexControlControl
StimulusSensory receptorAfferent pathIntegration centerEfferent pathEffector (target
cell/tissue)Response
Receptors (or Receptors (or Sensors)Sensors)
Different meanings for “receptor”: Different meanings for “receptor”: sensory receptor sensory receptor vs. vs. membrane receptormembrane receptor
Can be peripheral or central Can be peripheral or central
Constantly monitor environmentConstantly monitor environment
ThresholdThreshold (= minimum stimulus (= minimum stimulus necessary to initiate signal)necessary to initiate signal)
Fig 6-23
Afferent PathwayAfferent Pathway
From receptor to From receptor to integrating center integrating center
Afferent pathways of Afferent pathways of nervous system: ?nervous system: ?
Endocrine system has no Endocrine system has no afferent pathwayafferent pathway (stimulus comes directly (stimulus comes directly into endocrine cell)into endocrine cell)
Integrating CenterIntegrating Center
Neural reflexes usually in the CNS; endocrine integration in the endocrine cell itself
Receives info about change
Interprets multiple inputs and compares them with set-point
Determines appropriate response (→ alternative name: control center)
Efferent PathwayEfferent Pathway
From integrating From integrating center to effectorcenter to effector
NS NS electrical and electrical and chemical signalschemical signals
ES ES chemical signals chemical signals (hormones)(hormones)
EffectorsEffectors
Cells or tissues carrying out response
Target for NS:muscles and glands and some adipose
tissues
Target for ES:any cell with proper receptor
Responses Responses at 2 levels:at 2 levels:
1.1. Cellular response of target cell Cellular response of target cell opening of a channel Modification of an enzyme etc...
2.2. Systemic response at Systemic response at organismal levelorganismal level
vasodilation, vasoconstriction Lowering of blood pressure etc....
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 6-25
Fig 6-26
The Body’s 2 Control The Body’s 2 Control SystemsSystems
Variation in speed, specificity and duration of action
The two systems allow for 4 different types of biological reflexes
1. Simple (pure) nervous 2. Simple (pure) endocrine3. Neurohormone4. Neuroendocrine (different combos)
Fig 6-30
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