biol 373 uwaterloo lec 1
DESCRIPTION
biology 373 human physiology 2university of waterloolecture 1TRANSCRIPT
How will you be assessed?
Assumed BackgroundChapter 1 – intro to physiologycontrol systems and homeostasis
Chapter 2 – molecular interactionscellular chemistry, molecular bonds, biomolecules, acids / bases, protein interactions
Chapter 3 – membranes, cell anatomy / organelles
Chapter 4 – bioenergetics, cellular metabolismenzymes, ATP, gene transcription translation protein
Chapter 5 – membrane dynamicsdiffusion, active transport, carrier proteins, ion channels,endocytosis, osmosis, tonicity
Chapter 6 – cell-cell communicationsignal transduction, modulation of signal pathways
Outline of Rest of Intro Unit• What is physiology?
• Homeostasis
• Cell-cell communication revisited– signal transduction– modulation of signal pathways
• Homeostatic reflex pathways– Cannon’s Postulates– neural, endocrine and neuroendocrine reflex pathways
What is Physiology?
long answer:“the science of the mechanical, physical, bioelectrical, and biochemical functions of <organism of interest> in good health, their organs, and the cells of which they are composed”
short answer:“the science of the function of living systems”
Function and Process
• Function “why”– Why does the system exist?– Why does the event occur?
• Process “how” – How does a system work?
• physiological mechanisms
Homeostasis• maintenance of a relatively stable internal environment
(especially extracellular fluid)– oscillation around a set point
externalenvironment
intracellularfluid (ICF)
extracellular fluid (ECF)
Fig. 1.4
1854, Claude Bernard “la fixité du milieu intérieur”
1929, Walter Cannon “homeostasis”
‘homeo’ rather than homo similar, though not the same
Historical Interlude
published in 1932,$21 on amazon.ca
Walter Cannon 1871-1945
“flight or fight response”
- expanded on Bernard’s concept of homeostasis
Compensation fails
Internal changeresults in loss
of homeostasis
Organism inhomeostasis
Organism attemptsto compensate
Externalchange
Internalchange
Compensation succeeds
WellnessIllness or disease
Fig. 1.3
study of homeostatic mechanisms= physiology
failure to compensate for change= disease
study of failure to compensate= pathophysiology
Local versus Reflex Control
Brainevaluates the change and initiates a response.
Systemicchange in blood
pressure sensedhere.
Brain
LOCALCHANGE
LOCALRESPONSE
Blood vessels
REFLEXRESPONSE
initiated by cellsat a distant site.
cells near site of change initiate response.
cells at a distantsite control response.
Response
Stimulus
Integrating center
KEY
Fig. 1.8
Control Systems and Homeostasis
response loop:• stimulus, sensor, input signal, integrating centre, output
signal, target, response
feedback mechanisms:• negative feedback stabilizes variable• positive feedback reinforces stimulus – not homeostatic• feedforward control anticipates change
Response
Initialstimulus
Stimulus
Response
Initialstimulus
Stimulus
Response loopshuts off
Negative feedback: response counteractsstimulus, shutting off response loop
Positive feedback: response reinforces stimulus, sending variable farther from setpoint
Feedback cycleoutside factor isrequired to shut offfeedback cycle
Fig. 1.11
Cell-Cell Communication - Overview• 75 trillion cells in the human body
• homeostasis achieved by nervous and endocrine systems with their combination of electrical and chemical signals
– electrical signals – changes in membrane potential• restricted to nerve and muscle cells
– chemical signals are secreted into extracellular fluid by all cells• responsible for most communication
• cells that respond to signals are ‘target cells’
Cell-Cell Communication: long range
endocrine: chemical (‘hormone’) released into bloodstream and distributed throughout body
Fig. 6.114
Cell-Cell Communication: long rangeneural: electrical signal travels down neuron; reaches end and
is translated to chemical signal (neurotransmitter) which transmits information to next cell
neuro endocrine: electrical signal travels down neuron; reaches end and is secreted into blood
15
Fig. 6.1
What defines a ‘target’ cell?How can sending a signal throughout the entire body affect
only certain cells?
Only cells that have receptors for that signal will respond to it.signal molecule that binds to a particular receptor is its
ligand
Receptors are proteins thatproject to outside of the membrane, or are within the cell, in the cytoplasm
Chemical properties of signal molecules (ligands) determine what type of receptor they will interact with.
water soluble = hydrophilic = lipophobic surface receptorwater insoluble = hydrophobic = lipophilic intracellular receptor16
Location of Receptors
Lipophobic signal molecule
Receptor
Ligand-receptor complex
Rapid cellularresponses
Extracellular fluid
Intracellular fluid
Slower responsesrelated to changes
in gene activity
Receptor in cytosol
Receptorin nucleus
Lipophilic signalmolecules
Lipophobic signalmolecules
Cell membrane
Fig. 6.3a, b17
lipophilic = hydrophobic
lipophobic = hydrophilic
Types of Membrane Receptors
Cellmembrane
G protein
Channel Integrin
Enzyme
Anchorprotein
Cytoskeleton
Ionchannel
Enzyme-coupledreceptor
Integrinreceptor
G protein-coupledreceptor (GPCR)
18
Fig. 6.3c
Firstmessenger
Transducer
Secondmessengersystem
Targets
Signalmolecule
Membranereceptor protein
Intracellularsignal molecules
Targetproteins
binds to
activates
alter
create
Response Response
Fig. 6.5a
Signal Transduction
Signal Transduction
alter
signalmolecule
membrane receptor
signal transduction by proteins
amplifier enzymes
second messengermolecules
protein kinases Ca2+
phosphorylatedproteins
activated Ca2+-binding proteins
Extracellularfluid
Intracellularfluid
response
initiates
binds to
ionchannel
Fig. 6.5b20
Signal
Inactive A
Inactive B
Inactive C
Substrate
Conversion of substrateto product is the finalstep of the cascade.
Active A
Active B
Active C
Product
Fig. 6.6a
Signal Transduction Cascades
L
R
AE
Receptor-ligand complexactivates an
amplifier enzyme (AE).
One ligand is amplified into manyintracellular molecules.
Cellmembrane
ExtracellularFluid
IntracellularFluid
Fig. 6.6b
Signal transduction cascades provide amplification.
ATP
GTP
PI(membrane
phospholipid)
adenylylcyclase(membrane)
guanylyl cyclase(membrane)
guanylyl cyclase(cytosol)
phospholipase C(membrane)
GPCR
GPCR
enzyme-linkedreceptor
nitric oxide(NO)
activates proteinkinase A; binds to ion channels
activates proteinkinases
binds to ionchannels.
releases Ca2+ fromintracellular stores.
activates proteinkinase C
binds to calmodulin;binds to other proteins
phosphorylatesproteins; alterschannel opening
phosphorylatesproteins
alters channel opening
See Ca2+ effectsbelow.
phosphorylatesproteins
alters enzyme activity,exocytosis, musclecontraction, cyto-skeleton movement,channel opening
Ca2+
IP3
DAG
cyclic AMP
Ions
Lipid-derived
Nucleotides
SECONDMESSENGER
MADEFROM
AMPLIFIERENZYME
LINKEDTO ACTION EFFECTS
Components of Selected Signal Pathways
cyclic GMP
Fig. 6.6c
GPCR = G protein-coupled receptorIP3 = inositol trisphosphate; PI = phosphatidyl inositolDAG = diacylglycerol
see: 6.7, 6.8, 6.9, 6.11
Summary of Signal Transduction
Fig. 6.11
Modulation of Signal Pathways• one ligand may have several different types of receptors
– explains how same signal can have different effects in different cell types
• receptors exhibit saturation, specificity, competition for their ligands (and molecules similar to their ligands)– e.g. relative affinities of adrenergic receptors for epinephrine
versus norepinephrine– e.g. agonists and antagonists competing with endogenous
ligands
• cells can change their response to signals by changing receptor number or sensitivity– increase ↑ gene expression (up-regulation)– decrease internalize surface receptors (down-regulation)– change receptor sensitivity e.g. phosphorylation
25
More than one receptor for a particular ligand
Intestinalblood vessel
Skeletal muscleblood vessel
-Receptor response 2-Receptor response
Epinephrine + -Receptor
2-Receptor-Receptor
Epinephrine + 2-Receptor
Vessel constricts
Vessel dilates
ligand = epinephrine (fright or flight response)
Fig. 6.1326
Agonists and Antagonists
= natural (‘native’) ligand
structurally similar molecules may be able to compete for receptor binding sites
= similar molecule that activates receptor AGONIST; ANALOGUE; MIMIC
= molecule that is similar enough to native ligand to bind to receptor, but not activate it ANTAGONIST; BLOCKER
no responseresponse
27
similar to Fig. 6.14
28
Table 6.1
Many Diseases and Drugs Disrupt Signal Pathways
Cannon’s Postulates• the nervous system has a role in maintaining ‘fitness’
of the internal environment– coordinates responses that regulate blood volume,
blood pressure, osmolarity, body temp, etc
• some systems are under tonic control
• some systems are under antagonistic control
• one chemical signal can have different effects in different tissues“homeostatic agents antagonistic in one region of the body may be cooperative in another region”
‘Tonic’ Control
Time
Electricalsignals
fromneuron
Change in signal rate
TimeTime
Tonic control regulates physiological parameters in an up-down fashion.
Increased signal rate Decreased signal rate
Fig. 6.15a31
Antagonistic ControlAntagonistic neurons control heart rate:
some speed it up, while others slow it down.
Stimulation by parasympathetic nerves decreases heart rate.Stimulation by sympathetic nerves increases heart rate.
Heart beats Heart beats
Sympatheticneuron
Parasympatheticneuron
Fig. 6.15b32
Steps of a Reflex Pathway
SENSORor
RECEPTOR
AFFERENTPATHWAY
INTEGRATINGCENTER
EFFERENTPATHWAY
TARGET OREFFECTOR
RESPONSE
STIMULUS
Response loopFee
dbac
k lo
op
similar to Fig. 6.1633
sensors / detectors / receptors:• specialized cell types in strategic locations
(often in extracellular fluid)
examples of signals monitored:• chemicals - glucose, CO2, O2, Na+, Ca++
• hormones – via specific receptors
• osmolarity – cells that respond to swelling, shrinking
• blood volume/pressure – cells that respond to stretch
controller / integrating centre:• organ or gland• brain (often brain is cc’d but is not
necessary for homeostatic response
efferent output:• can be to particular cell type within an
organ or multiple organ systems
Fig. 6.17
Multiple Meanings of ‘Receptor’
A SimpleEndocrine Reflex
A Simple NeuralReflex
A Complex Neuro-endocrine Reflex
Response
Target
Target Target
Response Response
ReceptorReceptor
Internalor external
change
Internalor external
change
Internalor external
change
Input signal:sensory neuron
Input signal:sensory neuron
Endocrinesystem sensor-
integratingcenter
Nervoussystem
integratingcenter
Nervoussystem
integratingcenter
Output signal:hormone
Efferentneuron
Efferentneuron or
neurohormone
Endocrineintegrating
center
Output signal# 2: hormone
Fig. 6.18
Neural Versus Endocrine Control
Table 6.2
(Fig 6.19 – let’s come back to this one when we reach these types of pathways)