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