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Ch. 6: Communication, Ch. 6: Communication, Integration & HomeostasisIntegration & Homeostasis
Describe cell to cell communication
Explain signal transduction and signal pathways
Review homeostasis and its control pathways
Goals
Cell to Cell Cell to Cell CommunicationCommunication
75 trillion cells / 2 types of signals
4 basic methods of cell to cell communication:1. Direct cytoplasmic transfer2. Contact dependent signals (see IS discussion)
3. Short distance (local)4. Long distance (through combination of
signals)
Cell receiving signal = ?
Gap Junctions for Gap Junctions for Direct Signal TransferDirect 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
Local Communication Local Communication viaviaParacrines and Autocrines
(Chemical signals secreted by cells)
Mode of transport ?
Examples: Histamine, cytokines, eicosanoids
Many act as both
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 2) Nervous system uses electrical and chemical signals (APs vs. neurotransmitters and neurohormones)
Fig 6-2
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
Signal PathwaysSignal Pathways
Signal molecule (ligand)
Receptor
Intracellular signal
Target protein
Response
3 Receptor 3 Receptor LocationsLocations
Cytosolic or NuclearLipophilic ligand enters cell.
Often activates gene.Slower response.
Cell membraneLipophobic ligand cannot enter cell.
Outer surface receptor needed.
Faster response.Fig 6-4
Membrane Receptor ClassesMembrane Receptor Classes1. Chemically (ligand) gated channels
e.g.: nicotinic Ach receptor2. Receptor enzymes
3. G-protein-coupledSignal transduction
Direct Mechanisms via Chemically Direct Mechanisms via Chemically Gated Channel: Gated Channel: Nicotinic ACh Nicotinic ACh receptorreceptor
Change in ion permeability changes membrane potential
Signal Transduction
Activated receptor alters intracellular molecules to create response
First messenger transducer amplifier second messenger Fig 6-8
Most Signal Transduction uses G-Most Signal Transduction uses G-Protein Protein
100s of G protein-coupled receptor types known
G protein is membrane transducer (binds GDP / GTP name!)
Activated G proteins 1. open ion channels, or2. alter intracellular enzyme activity, e.g.:
via adenyl cyclase (amplifier) cAMP (2nd messenger) protein kinase activation
Novel Signal Molecules: Novel Signal Molecules: CaCa2+2+
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
Gases and Lipids as Signal Gases and Lipids as Signal MoleculesMoleculesNO 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.
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)
CompetitionAberrations in signal transduction _____________ (table 6-3)
Many drugs target signal transduction (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
Control Pathways: Control Pathways: Response and Feedback Response and Feedback
LoopsLoops
Cannon's Postulates (concepts) of properties of homeostatic control systems
1. Nervous regulation of internal environment
2. Tonic level of activity → “how much?”, not ON or OFF - regulated by nerve signal frequency
3. Many systems have antagonistic controls (insulin/glucagon)
4. Chemical signals can have different effects on different tissues
Failure of homeostasis?
Fig 6-20
Maintenance of Homeostasis
Via local or long distance pathways
Local: autocrines and paracrines
Long-distance: reflex control◦ Nervous ◦ Endocrine◦ both
Steps of Reflex ControlSteps of Reflex Control
Stimulus
Sensory receptor
Afferent path
Integration center
Efferent path
Effector (target cell/tissue)
Response Fig 6-23
Receptors (or Sensors)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
Afferent Afferent PathwayPathway
From receptor to integrating center
Afferent pathways of nervous system: ?
Endocrine system has no afferent pathway (stimulus comes directly into endocrine cell)
Integrating Integrating CenterCenter
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
Efferent PathwayEfferent Pathway
From integrating center to effector
NS electrical and chemical signals
ES chemical signals (hormones)
EffectorsEffectors
Cells or tissues carrying out response
Target for NS: _________________________________
Target for ES:__________________________________
Response Loops Begin with Response Loops Begin with Stimulus – End with Response Stimulus – End with Response
Response takes place at 2 levels
1. Cellular response of target cell ◦ Opening of a channel◦ Modification of an enzyme etc...
2. Systemic response at organismal level
◦ Vasodilation, vasoconstriction◦ Lowering of blood pressure etc....
Feedback Loops Modulate the Response
LoopResponse 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 6-27
Fig 6-26
The Body’s 2 Control The Body’s 2 Control SystemsSystems
Variation in speed, specificity and duration of action
Compare the different types of reflexes (Table 6-5)
1. Simple (pure) nervous 2. Simple (pure) endocrine3. Neuro-hormone4. Neuro-endocrine (different combos)
Fig 6-31