Post on 10-Jun-2020
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Cellular Messengers
Intracellular Communication
1. Paracrines• Local messengers (neighboring cells)
Distributed by simple diffusionHistamine (local vasodilator)
Most common cellular communication is done through extracellular chemical messengers:
Ligands
Specific in function
2. Neurotransmitters• Short-range chemical messengers in response to
electrical stimulusAcetylcholine
3. Hormones• Long-range chemical messengers secreted by
endocrine glands in response to a signalNeed target cells
4. Neurohormones• Released by neurosecretory neurons
Stimulated by electric impulse, but transmits a chemical messenger
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Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone
Gap junctions
Transient direct linkup of cells
Figure 3.7 (1)Page 65
Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone
Paracrine secretion
Secretingcell
Localtargetcell
Neurotransmitter secretion
Electrical signal
Secreting cell(neuron)
Localtarget cell
Figure 3.7 (2)Page 65
Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone
Hormonal secretion
Blood
Secreting cell(endocrine cell)
Distant target cell
Nontarget cell(no receptors)
Figure 3.7 (3)Page 65
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Small molecules and ions Paracrine Neurotransmitter Hormone Neurohormone
Neurohormone secretion
Electrical signal
Secreting cell(neuron)
Blood
Distant target cell
Nontarget cell(no receptors)
Incoming signals are accepted through process of signal transduction
Extracellular chemical messenger binding with a receptor (first messenger)
• Process occurs to:
1. Open or close specific channels for ion regulation
2. Transfer signal to intracellular messenger (second messenger)
Membrane channels receiving chemical messengers:
1. Leak channels• Open all the time (ions “leaking” out or in)
2. Gated channels (chemical & voltage) • Must be triggered to open & require at least one of the
following:1. Binding to specific membrane receptor to the channel2. Change in electrical status of the membrane3. Stretching or mechanical deformation
G proteins• Intermediaries that are activated by binding of
messengers (cause channels to open)
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Channel regulation (open or closed) regulates ion flow
• Nerve conduction• Muscle contraction (Ca2+)
Second messenger pathways:
2 major pathways1. Cyclic adenosine monophosphate (cyclic AMP
or cAMP)2. Calcium
Plasmamembrane
ECF
(Binding of extracellularmessenger to receptoractivates a G protein, theα subunit of which shuttlesto and activates adenylylcyclase)
(Phosphorylates)
(Phosphorylation inducesprotein to change shape)
(Activates)Second messenger
Receptor
G proteinintermediary
Firstmessenger, anextracellularchemicalmessenger
= phosphate
ICF(Converts)
Adenylylcyclase
Figure 3.8 Page 68
First messenger, an extracellularchemical messenger
Plasma membrane
ECF
(Activates)Second messenger
ICF
Receptor(Binding of extracellularmessenger to receptoractivates a G protein,the α subunit of whichshuttles to and activatesphospholipase C)
PIP2DAGIP3
= Phosphatidylinositol bisphosphate= Diacylglycerol= Inositol trisphosphate
(PIP2 converted byphospholipase C toDAG and IP3)
(Mobilizes)
(Induces proteinto change shape)
G protein intermediary
Phospholipase C
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Molecules in secondmessenger system
Total numberof molecules
Cyclic AMP (100) 1,000
Amplification
Phosphorylated (activated) protein(e.g., an enzyme) 100,000
Amplification
(100)
Products ofactivated enzyme 10,000,000
Amplification
(100)
Extracellular chemical messenger bound to membrane receptor
1
Activatedadenylyl cyclase
Amplification
(10) 10
Activatedprotein kinase 1,000
Figure 3.10 Page 72
Transport Mechanisms
Membrane permeability:
1. Solubility of the particle in lipid• Uncharged (nonpolar) molecules (O2, CO2)
2. Size of particle
Does not mean large charged particles cannot cross
• Glucose?
Active & passive forces at work!
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Fick’s Law of Diffusion
1. Magnitude of concentration gradient
2. Permeability of membrane to substance
3. Surface area for where diffusion takes place
4. Molecular weight of the substance
5. Distance of diffusion
If a substance canpermeate the membrane:
If the membrane isimpermeable to a substance:
Figure 3.12 Page 73
Passive diffusion:
1. Concentration gradient
2. Electrical gradient
3. Osmosis• Water movement through aquaporins• Net diffusion of water
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Diffusion from area Ato area B
Net diffusion(diffusion from area Ato area B minus diffusionfrom area B to area A)
Diffusion from area Bto area A
= Solute molecule
Figure 3.11 (1) Page 73
Diffusion along concentration gradient (Passive)
= Solute molecule
No net diffusion(diffusion from area Ato area B equals diffusionfrom area B to area A)
Diffusion from area Ato area BDiffusion from area Bto area A
Positivelycharged area
Negativelycharged area
Cations (positively charged ions)attracted toward negative area
Anions (negatively charged ions)attracted toward positive area
Figure 3.13 Page 75
Movement along an electrical gradient
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100% water concentration 0% solute concentration
90% water concentration 10% solute concentration
= Water molecule = Solute molecule
Figure 3.14 Page 75
Osmosis
Membrane
Higher H2Oconcentration,lower soluteconcentration
Lower H2Oconcentration,higher soluteconcentration
= Water molecule = Solute molecule
H2O
Membrane (permeable to both water and solute)
Side 1 Side 2
• Water concentrations equal• Solute concentrations equal• No further net diffusion• Steady state exists
H2O moves from side 1 to side 2down its concentration gradient
Solute moves from side 2 to side 1down its concentration gradient
Side 1 Side 2
= Water molecule
= Solute molecule
Higher H2O concentration,lower solute concentration
H2O
Lower H2O concentration,higher solute concentration
Solute
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= Water molecule
= Solute molecule
Membrane (permeable to H2O but impermeable to solute)
Lower H2O concentration,higher solute concentration
H2O moves from side 1 to side 2down its concentration gradient
• Water concentrations equal• Solute concentrations equal• No further net diffusion• Steady state exists
Solute unable to move from side 2 toside 1 down its concentration gradient
Side 1 Side 2
Side 1 Side 2
Originallevel ofsolutions
Higher H2O concentration,lower solute concentration
H2O
= Water molecule= Solute molecule
Side 1 Side 2
Hydrostatic(fluid)pressuredifference
Osmosis
Hydrostatic pressure
Active or assisted diffusion:
1. Specificity
2. Saturation
3. Competition
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1. Facilitated diffusion (no energy requirement)• Uses carrier to assist substance• High concentration to low concentration
Glucose
2. Active transport• Uses carrier to travel against concentration
gradient• ATP
Step 1
Phosphorylatedconformation Yof carrier
Step 2
Direction oftransport
Concentrationgradient
Dephosphorylatedconformation Xof carrier
Molecule to betransported
Figure 3.21 Page 82
= phosphate
(High)
(Low)ICF
ECF
Na+
Na+-K+pump• Na+-K+ATPase pump
Transports Na+ out into ECFPicks up K+ from ECF and brings it into ICF
• 3 Na+ out, 2 K+ in
3 important roles:1. Establishes concentration gradient (nerve cell
function)2. Regulates cell volume3. Energy used is a co-transport (secondary active
transport)Glucose and AA across intestinal and kidney cells
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= Sodium (Na+) = Potassium (K+) = Phosphate
ICF
ECF
Lumen ofintestine
Luminal border
Epithelial cell liningsmall intestine
Tightjunction
Blood vessel
= Sodium = Potassium = Glucose = Phosphate
No energyrequired
Cotransport carrier
Figure 3.23Page 84
Glucose carrier
Na+–K+ pump
No energyrequired
Energyrequired
Membrane Potential
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Membrane potential (polarized):
• Separation of charges across the membrane
1. Created by cations and anions in ICF & ECF
2. Millivolt (mV): 1mV = 1/1000volt
• Energy required to keep charges separated, allowing a “potential” for doing work
Membrane
Membrane has no potential
Figure 3.25 (1) Page 87
Membrane
Membrane has potential
Figure 3.25 (2) Page 87
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Membrane
Figure 3.25 (3) Page 87
Separated chargesresponsible forpotential
Remainder offluid electricallyneutral
Remainder offluid electricallyneutral
Figure 3.25 (4) Page 87
Plasma membrane
Resting membrane potential:
Ions responsible (Na+, K+ and A-(intracellular proteins))
0650A-
50-751505K+
115150Na+
PermeabilityICECIon
Maintained by Na+-K+ pump (20%)
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Plasma membrane
ECF ICF
Concentrationgradient for K+
Electricalgradient for K+
EK+ = –90 mVFigure 3.26 Page 89
Plasma membrane
ECF ICF
Figure 3.27 Page 90
Concentrationgradient for Na+
Electricalgradient for Na+
ENa+ = +60 mV
Plasma membrane
ECF ICF
Figure 3.28 Page 91
Resting membrane potential = –70 mV
Relatively large netdiffusion of K+
outward establishesan EK+ of –90 mV
No diffusion of A–across membrane
Relatively small netdiffusion of Na+
inward neutralizessome of thepotential created byK+ alone
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ICF
ECF
(Passive)
(Passive)K+ channelNa+ channel
Na+–K+
pump (Active)
(Active)
Figure 3.29 Page 9280%20%