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

Activated G-protein Opens Ion Channel

Muscarinic ACh receptor

Activated G-protein Alters IC Enzyme Activity

Compare to Fig 6-11

Epinephrine Signal Transduction

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

Diabetes mellitus