8 - Communication, Integration & Homeostasis

Main Patterns of Physiological Communication (3)

1. Simple diffusion across small distances

2. Widespread distribution of molecules through the circulatory system

3. Rapid, specific delivery of messages by the nervous system

Main types of Physiological Communication (2)

1. Electrical (causes change in cells’ membrane potential)

2. Chemical ( molecules secreted into the ECF)

Gap Junctions (Cell-cell communication)

Direct cytoplasmic transfer of electrical/chemical signals between adjacent cells

• Protein channel creates bridge between adjacent cells (forms from the union of connexins on two adjacent cells - membrane-spanning proteins)

• Allows transfer of amino acids, ATP, etc.

• Electrical signals can pass directly cell to cell

• Channels can open or close

• Multiple open channels can allow several cells to act together as one multi-nucleated cell (know as syncytium)

Contact Dependent Signals (cell-to-cell communication)

Surface molecules on one cell’s membrane binds to the surface molecules on another cell’s membrane

• Cell adhesion molecules (CAMs) act as receptors in cell-cell signalling

• Linked to the cytoskeleton or intracellular enzymes

Secretory signals (cell-to-cell communication)

Cell releases chemicals that diffuse through ECF and act on those close by (paracrine signalling) or on cell that released them (autocrine)

• NOT HORMONES, just chemicals being secreted to neighbouring cells

Long Distance Communication (cell-to-cell communication)

Involves nerves and/or blood for transportation

• Hormones: chemical signals that are secreted into the blood & distributed all over the body via circulation (blood vessels)

• Neurocrine System: the nervous system uses a combination of chemical signals & electrical signals to communicate over long distances.

  • An electrical signal travels along a nerve cell until it reaches the very end of the cell, where it is translated into a chemical signal secreted by the neuron

Cytokines

Associated primarily w/ immune responses, such as inflammation, but also control cell development & cell differentation.

• In development and differentiation, cytokines usually function as autocrine or paracrine signals

• In stress & inflammation, some cytokines may act on relatively distant targets & may be transported through the circulation just as hormones are

Cytokines vs Hormones

Cytokines:

• any nucleated cell can secrete cytokines at some point in its life span

• made on demand

• Intracellular signal pathways usually different

Hormones:

• produced by specialized endocrine glands/epithelial cells

• made in advanced & stored in the endocrine cell until needed

Receptor Proteins

A cell can respond to a particular chemical signal only if the cell has the appropriate receptor protein to bind that signal

• If a target cell has the receptor for a signal molecule, binding of the signal molecule to the receptor protein initiates a response

Signal Pathway Steps (5)

1. Signal molecule (ligand) binds to a protein receptor

2. Activation of receptor by ligand

3. Receptor activates one or more intracellular signal molecules

4. last molecule in the pathway initiates synthesis of target proteins or modifies existing target protein for response

5. Negative feedback

• Target cell receptor proteins may be found in the nucleus, the cytosol, or on the cell membrane as integral proteins

Lipophobic Signal (signal receptor)

Bind to the surface membrane receptors and produce effects through a second-messenger system/cascade

• Hates lipids, likes H₂O (doesn’t want to bypass the lipid bilayer)

• Last messenger of cascade acts on intracellular targets to create response

• Response can include changes to/creation of:

  • an enzyme

  • muscle contraction

  • cytoskeletal movement

  • change in protein synthesis

  • alteration of membrane transport

Rapid cellular responses

Lipophilic Signal (signal receptor)

Ligand diffuses through lipid membrane to bind with intracellular receptors

• Likes lipids (wants to bypass the lipid bilayer

• Binds to receptor in the cell or nucleus

• Activates a specific gene that contains code for synthesizing a particular enzyme

• Transcription to mRNA, which leaves nucleus & enters cytoplasm

• Binds with ribosomes to direct synthesis of new proteins (& ultimately physiological response)

Slower responses related to changes in gene activity

4 Major Lipophobic Signal Receptor Types

1. Receptor channels: chemically gated channels that open when the receptor binds

2. Receptor enzymes

3. G protein coupled receptors

4. Integrin Receptors

   1. Last 3: signal is passed across membrane to initiate intracellular response (like a telephone call)

Receptor Channels (Lipophobic receptor types)

• The activation of receptor-channels initiates the most rapid intracellular responses of a receptors

• When an extracellular ligand binds to the receptor-channel protein, a channel gate opens or closes, altering the cell’s permeability to an ion

• Increasing or decreasing ion permeability rapidly changes the cell’s membrane potential, creating an electrical signal that alters voltage-sensitive proteins

Receptor Enzymes (Lipophobic receptor types)

Catalytic receptors that have 2 regions:

• A receptor region on the extracellular side of the cell membrane

• An enzyme region on the cytoplasmic side

• Ligand binding to the receptor activates the intracellular enzyme

• Catalytic receptor enzymes include protein kinases

G-Protein Coupled Receptors (Lipophobic receptor types)

• Crosses the phospholipid bilayer seven times

• The cytoplasmic tail of the receptor protein is linked to a three-part membrane transducer molecule known as a G protein

• Inactive G proteins are bound to guanosine diphosphate (GDP)

• Exchanging the GDP for guanosine triphosphate (GTP) activates the G protein

• When G proteins are activated, they either

  • Open an ion channel in the membrane or

  • Alter enzyme activity on the cytoplasmic side of the membrane

Integrin Receptors (Lipophobic receptor types)

• On the extracellular side of the membrane, integrins bind either to proteins of the extracellular matrix or to ligands such as antibodies & molecules involved in blood clotting

• Inside the cell, integrins attach to the cytoskeleton via anchor proteins

• Ligand binding to the receptor causes integrins to activate intracellular enzymes or alter the organization of the cytoskeleton

  • Cell adhesion, activate immune cells, & cell movement

Signal Transduction

The process by which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response

• The extracellular signal molecule is the first messenger, & the intracellular molecules form a second messenger system

1. An extracellular signal molecule ( the first messenger) binds to & activates a membrane receptor

2. The activated membrane receptor turns on its associated proteins and starts an intracellular cascade of second messengers

3. The last second messenger in the cascade acts on intracellular targets to create a response

Second Messenger system amplifies the response; T or F?

True

Calcium (Ca²⁺) (Key signal molecules)

• Can enter the cell through a wide variety of channels, mostly stored in endoplasmic reticulum (ER)

• Can also be released from intracellular compartments by second messengers

• Functions:

  • Alter enzyme/transporter activity, channel gating

  • Movement of contractile proteins (cytoskeleton)

  • Trigger exocytosis of secretory vesicle

  • Initiate development of embryo when egg is fertilized

  • Muscle contraction

Soluble Gases (Key signal molecules)

• Short-acting paracrine/autocrine signal molecules that act close to where they are produced

• Includes Nitric Oxide (NO), carbon monoxide (CO), & hydrogen sulfide (HS)

Nitric Oxide (Key signal molecules)

• Produced by endothelial cells lining blood vessels

• Causes smooth muscle cells to relax & blood vessels to dilate

• Also acts as neurotransmitters and neuromodulator in the brain

Carbon monoxide (CO)

• Activates guanylyl cyclase and cGMP, but may also work independently to exert its effects

• Carbon monoxide targets smooth muscle & neural tissue

Hydrogen Sulfide (H₂S)

Acts in the cardiovascular system to relax blood vessels

Eicosandoids

lipid-derived paracrine signals that play important roles in many physiological processes

• Derived from arachidonic acid, a 20-carbond fatty acid

• Act on their target cells using G protein-coupled receptors

• The synthesis process for eicosanoids is a network called the arachidonic acid cascade

Properties of Receptors

Receptors behave like all other proteins:

• Specificity - certain ligands can only bind to specific receptors

• Competition - ligands w/ similar structure can bind to the same receptor

• Saturation - a point is reached where all receptors are bound

Receptor Agonists & Antagonist

Down-regulation

Target cell decreases in receptor #

• Removal from membrane (endocytosis) or receptor desensitization

Up-regulation

Target cell inserts more receptors into the membrane

• Allows cells to carry responsiveness to signal molecules

Stopping the Signal

• Ligand can be degraded by enzymes in extra-cellular space

• Chemical messengers can be taken up into neighbouring cells

• Endocytosis of receptor-ligand complex (receptor returned by exocytosis)

  • Bottom line: process initiated by signal can be stopped when necessary

In more complicated reflex control pathways, info must be transmitted throughout the body using chemical signals or a combination of electrical & chemical signalling; T or F?

True

Regulated Variables & Control Systems

1. The nervous system has a role in preserving the “fitness” of the internal environment

2. Some systems of the body are under tonic control

3. Some systems of the body are under antagonistic control

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

Reflex Pathways

• Usually involves chemical & electrical signals (nervous & endocrine control)

• Response loop has 3 main components

  • Input signal

  • Integration of Signal

  • Output signal

1) Stimulus (Steps in a Reflex Pathway)

Starts the reaction

• Can be changes in temp, oxygen, blood pressure, etc. (any regulated variable)

• E.g. body temp control on a hot day

2) Sensory Receptors (Steps in a Reflex Pathway)

Located throughout the body sense change in stimulus

• Central receptors - located in or closely related to the brain (eyes, ears, nose, tongue, central, chemo-, osmo-, & thermoreceptors)

• Peripheral Receptors - found elsewhere in the body (joints, skin, blood vessels, etc.), for pH, osmolarity, temp, pressure, etc.

• E.g. Increase in body temp sensed by thermoreceptors

3) Activated Sensor (Steps in a Reflex Pathway)

sends input signal to integrating centre (usually CNS)

• E.g. thermoreceptors send message to hypothalamus

4) Integration centre (Steps in a Reflex Pathway)

compares input signal to desired setpoint

• E.g. hypothalamus assesses if body temp is >37 degrees

5) Output signal (Steps in a Reflex Pathway)

If signal is out of range, integrating centre initiates output signal

• E.g. Hypothalamus sends message to skin, muscle & sweat glands

6) Output signal to target (Steps in a Reflex Pathway)

Output signal travels to the target (effector)

7) Response (Steps in a Reflex Pathway)

Effector carries out response to bring variable back to normal

• Responses can be cellular or systemic

• E.g. Arterioles dilate, muscles relax, sweating starts, body temp decreases

Summarized Steps in a Reflex Pathway

1. Stimulus occurs

2. Sensory receptors sense change

3. Activated sensor sends input signal to integrating centre (afferent signal)

4. Integrating centre compares input signal to desired set-point

• These 4 steps are always active - always looking for small changes & sending it to the integrating centre to sense if the change is within homeostasis

5. If signal is out of range, integrating centre sends output signal (efferent signal)

6. Output signal travels to the target (effector)

7. Target carries out response to bring variable back to normal

Nervous System vs. Endocrine System

• Reflex control can be done by one system or both

• Nervous & endocrine systems often overlap (neuroendocrine)

Specificity

• Nervous system:

  • Each neuron has a specific target cell

• Endocrine system:

  • Chemical messengers reach many cells through the blood (moves around the whole body)

  • Receptors determine response

  • Several tissues can respond to the same hormone

Nature of the signal

• Nervous system:

  • Electrical (neurons) & chemical (neurotransmitters)

• Endocrine system:

  • Purely chemical (hormones) & larger

Speed:

• Nervous system:

  • Very fast (electrical signals up to 120m/sec)

• Endocrine system:

  • Slower

  • Requires distribution through circulatory system and diffusion from capillaries to receptors

Duration of Action

• Nervous system:

  • Relatively short

  • Neurotransmitters rapidly removed from vicinity of action

  • Sustained response requires multiple neural signals

• Endocrine system:

  • Last longer

  • Controls “longer” processes like metabolism and reproduction

Coding for Stimulus Intensity

• Nervous system:

  • Signal strength is constant

  • Intensity of response depends on signal frequency

  • There’s always a space between responses (gives the cell a rest)

• Endocrine system

  • Stimulus intensity is proportional to hormone release

Simple vs Complex Control Pathways

Simple Control Pathway

• Generally have one integrating centre

  • Direct response to a single stimulus

  • Can be either neural or hormonal

• Complex control

  • Involves more than one integrating centre

  • Can involve both neural and hormonal (endocrine control)

  • Typically symbolized by the brain