Physio 1, Fall ’08, LPC

Chapter 6 – Communication, Integration, and Homeostasis

I – Cell-to-Cell Communication
Electrical signals

Gap junctions
Long distance communication

Chemical signals

Gap junctions
Contact dependent signals
Local communication
Long distance communication

Local Communication

Gap junctions – cytoplasmic connection between adjacent cells

Small molecules can pass -> chemical signal transferred
Electrical signals can pass

Contact-Dependent Signals – surface molecules on one cell membrane bind to a membrane protein on another

Paracrine – chemical signal from one cell acts on another that is quite close

Autocrine – chemical signal from one cell acts on itself

Distant Communication

Hormones – chemicals secreted by endocrine glands, act on cells with receptors

Neurotransmitters – chemicals secreted by nerves, act on nearby target (Usually another nerve or a muscle) (Nerve cells also use electrical signals for transmitting messages)

Neurohormones – chemicals released by neurons into blood, act on distant cells with receptors

II – Signal Pathways
Introduction

1. Signal protein = ligand, binds to receptor
2. Ligand-receptor binding activates receptor
3. Receptor activates one or more intracellular signal molecules
4. Last signal molecule in pathway creates response

Intracellular Receptors

Lipophilic
Bind to cytosolic receptor or nuclear receptors
Nuclear receptors -> mRNA -> protein synthesis

Lipophobic Receptors

Bind to receptor proteins on cell membrane
4 types

1. Ligand-gated ion channels – opens or closes channel & alters ion flow across membrane

Rapid
Often located in nerve & muscle

Can respond to G proteins or intracellular 2nd messenger

Other 3 transduce and amplify signal

Signal transduction

a. binding activates receptor
b. activated receptor

a. activates protein kinase that phosphorylates a protein OR
b. activates an enzyme that creates 2nd messenger

c. 2nd messenger may

a. alter gating of ion channels, -> electrical signal  OR
b. increase intracellular Ca++, -> bind to proteins, changes their function OR
c. change enzyme activity, -> response

d. proteins modified by Ca++ binding and phosphorylation control:

a. metabolic enzymes
b. motor proteins for muscle contraction & cytoskeletal movement
c. proteins that regulate gene activity & protein synthesis
d. membranes transport & receptor proteins

Signal amplification – Ligand binding -> amplifier enzyme, -> activation of several more molecules

2. Receptor enzymes

Outer region binds ligand
Cytoplasmic region is either a protein kinase or guanylyl cyclase (GTP -> cGMP)

3. G protein-coupled receptors

(Spans cell membrane 7 times)
cyctoplasmic tail = G protein
activated G protein

opens ion channel OR
alters enzyme activity, -> amplifier enzymes

1. phospholipase C OR
2. adenylyl cyclase – converts ATP to cAMP, cAMP phosphorylates other intracellular proteins

4. Integrin receptors - affect cytoskeleton OR activate intracellular enzymes

III - Calcium as a Signal Molecule

Ca++ enters cytosol through voltage-, ligand- or mechanically gated channels or released from intracellular stores
Ca++ combines with cytoplasmic Ca++ binding proteins to

alter enzyme or transporter activity or the gating of ion channels OR
alter movement of contractile or cytoskeletal proteins OR
trigger exocytosis of secretory vesicles OR
bind directly to ion channels , -> alters gating state OR
Ca++ entry into a fertilized egg initiates development of embryo

IV – Modulation of Signal Pathways

Receptors exhibit saturation, specificity & competition (same as enzymes)
Receptors are specific, but can compete for similar ligands
Receptors are tissue specific. Same ligand may -> different response in different tissues.

Agonists – activate receptor
Antagonist – blocks receptor

Up-regulation – if ligand scarce, cells will become more sensitive to it or increase number of receptors
Down-regulation – if ligand overly abundant, cells will react less or decrease number of receptors

Terminating signal

Endocytosis of receptor-ligand complex
Remove or degrade 1st messenger

V – Control Pathways

Bodily processes need to be controlled variably because conditions inside and outside body change

Regulated variables & physiological control systems

1. Nervous system – detects and controls some factors
2. Tonic control of some systems = continuous control, sometimes more stimulation, sometimes less

3. Antagonistic control – two opposing controls to maintain homeostasis

4. One chemical signal can have different effects in different tissues

Local or Long-distance Pathways

Local control – paracrine and autocrine signals

Long distance pathway = reflex

Uses nervous, endocrine or both systems
Respond to widespread or systemic changes
Input (stimulus) -> sensor or receptor -> afferent pathway -> Integrating center -> efferent pathway -> target or effector -> Response

Stimulus – disturbance or change

Receptor – specialized cells that respond to change, have threshold

Afferent pathway - electrical or chemical in reflex, none in endocrine because endocrine cell is both sensor and integrator

Integrating center

Receives information about change, sorts it, initiates response
Reflex – usually CNS
Endocrine – endocrine cell

Efferent pathway

Nervous – electrical and chemical signals via efferent neuron
Endocrine – hormones travel through blood to target

Effectors – cells or tissues that carry out response ( ex = muscle)

Response – cellular and systemic

Comparison of endocrine, neural and neuroendocrine control pathways – fig 6-30

Setpoints can be varied

Feedback loops

Negative feedback loop – response opposes or removes the signal, maintains homeostasis

Positive feedback loop – response enforces stimulus, requires intervention or even outside loop to stop response

Feedforward control anticipates change.

Table 6-4 – learn specificity, nature of signal, speed, duration of action, coding for stimulus intensity in Neural Reflex vs Endocrine Reflex

Reflexes can be simple or complex (may be more than one integrating center)

Table  6-5 – learn sensor or receptor, afferent pathway, integrating center, efferent pathway, effector(s) and response in neural, neuroendocrine and endocrine reflexes