1

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

2

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

3

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)

4

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!

6

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

9

= 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%