Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

40
Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology

Transcript of Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Page 1: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Topic 3

The Neuronal Membrane at Rest

Lange

Biology 463 - Neurobiology

Page 2: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Introduction

Resting Potential – the chemical makeup of the neuron when it is at “rest”…. meaning there is no message present

Action Potential – the chemical makeup of the neuron when it is “active”…. meaning there is a message present

Please note that the image above displays neurons in a way that can perpetuate a misconception: The Action Potential does NOT occur throughout the entire neuron instantly, but instead… the Action Potential will exist in a small portion of the neuron and will travel along the length of the neuron.

Page 3: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

The Cast of Chemicals Involved the Generation of an Action Potential

• Cytosolic and Extracellular Fluids– water is a polar solvent– Various cations (+) and anions (-)

Page 4: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• The Phospholipid Membrane– Hydrophilic (Polar) Head

• Materials that dissolve in water will pass through – Hydrophobic (Nonpolar) Tails

• Materials that dissolve in water will NOT pass through• Materials that dissolve in non-polar solvents (such as oils)

will pass through

Page 5: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

– The phospholipids will aggregate in a water media to create what is known as the Phospholipid Bilayer

Page 6: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

With the phospholipid molecule having the polar head region and the nonpolar tail region, when the phospholipid bilayer (PLB) is formed, the property that is seen is a PLB that serves as a selectively permeable membrane… a crucial feature for message transport both in the “electrical message” and the chemical message aspect of the neuron.

Page 7: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• Proteins

– Molecules

• Enzymes

• Cytoskeletal elements

• Receptors

• Specialized transmembrane proteins

– Control resting and action potentials

It is estimated that there can be hundreds of billions of different types of proteins that can be made, and our best estimate is that there are roughly 100,000 different proteins produced and used in the human body.

Page 8: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• Protein structure is enormously diverse:

• The 20 different amino acids consisting of an alpha carbon, a carboxyl group, hydrogen, and some sort of R (residue) group

• Diversity is due to the variation in the R group

Page 9: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

In the neuron, proteins are synthesized by ribosomes in two primary areas:

– Neuronal cell body (soma)– Axon terminals

In both places, the ribosomes assemble amino acids into polypeptide chains (connected by polypeptides)

Page 10: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Levels of protein structure.

Secondary structure:The primary chain formsspirals (-helices) andsheets (-sheets).

Tertiary structure:Superimposed on secondary structure.

-Helices and/or -sheets are folded upto form a compact globular moleculeheld together by intramolecular bonds.

Quaternary structure:Two or more polypeptide chains, eachwith its own tertiary structure, combineto form a functional protein.

Tertiary structure of prealbumin(transthyretin), a protein thattransports the thyroid hormonethyroxine in serum and cerebro-spinal fluid.

Quaternary structure of afunctional prealbumin molecule.Two identical prealbumin subunitsjoin head to tail to form the dimer.

Amino acid Amino acid Amino acid Amino acid Amino acid

-Helix: The primary chain is coiledto form a spiral structure, which isstabilized by hydrogen bonds.

-Sheet: The primary chain “zig-zags” backand forth forming a “pleated” sheet. Adjacentstrands are held together by hydrogen bonds.

(a) Primary structure: The sequence of amino acids forms the polypeptide chain.

(b)

(c)

(d)

Page 11: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

(a) Primary structure: The sequence of amino acids forms the polypeptide chain.

Amino acid Amino acid Amino acid Amino acid Amino acid

Page 12: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

-Helix: The primary chain is coiledto form a spiral structure, which isstabilized by hydrogen bonds.

-Sheet: The primary chain “zig-zags” backand forth forming a “pleated” sheet. Adjacentstrands are held together by hydrogen bonds.

(b) Secondary structure:The primary chain forms spirals (-helices) and sheets (-sheets).

Page 13: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Tertiary structure of prealbumin(transthyretin), a protein thattransports the thyroid hormonethyroxine in serum and cerebro-spinal fluid.

(c) Tertiary structure: Superimposed on secondary structure. -Helices and/or -sheets are folded up to form a compact globular molecule held together by intramolecular bonds.

Page 14: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Levels of protein structure.

Quaternary structure ofa functional prealbuminmolecule. Two identicalprealbumin subunitsjoin head to tail to formthe dimer.

(d) Quaternary structure: Two or more polypeptide chains, each with its own tertiary structure, combine to form a functional protein.

Page 15: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

An example of the progression in complexity of structure in proteins with the final quaternary structure being that of hemoglobin.

Page 16: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.
Page 17: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Proteins develop in a variety of forms in neurons to form

– Ion channels using channel proteins

– Ion pumps using other proteins

Page 18: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

The Movement of Ions

• Simple diffusion is an option for small ions and other small molecules

Page 19: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• Electrical current influences ion movement

• Electrical conductance (g) and resistance (R);

R = 1/g

• Electrical potential (voltage)

Electricity and Circuits

Page 20: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Chemicals Involved in the Conduction of Electricity• Electricity

– Electrical current can flow across a membrane

– Ohm’s law I = gV (current = conductance x electrical potential)

Page 21: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

The Ionic Basis of The Resting Membrane Potential

• Membrane potential: Voltage across the neuronal membrane

Page 22: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• Equilibrium Potential (Eion) – No net movement of ions

when separated by a phospholipid membrane

– Equilibrium reached when K+ channels inserted into the phospholipid bilayer

– Electrical potential difference that exactly balances ionic concentration gradient

Page 23: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• Equilibrium Potential

Page 24: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Voltmeter

Microelectrodeinside cell

Plasmamembrane

Ground electrodeoutside cell

Neuron

Axon

Page 25: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Depolarizing stimulus

Mem

bra

ne

po

ten

tial

(vo

ltag

e, m

V)

Time (ms)

0–100

–70

0

–50 –50

+50

1 2 3 4 5 6 7

Hyperpolarizing stimulus

Mem

bra

ne

po

ten

tial

(vo

ltag

e, m

V)

Time (ms)

0 1 2 3 4 5 6 7–100

–70

0

+50

Insidepositive

Insidenegative

(a) (b)

Restingpotential

DepolarizationRestingpotential

Hyper-polarization

Page 26: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

(b)

Depolarized region Stimulus

Plasmamembrane

Depolarization Spread of depolarization(a)

Page 27: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Distance (a few mm)

–70Resting potential

Active area(site of initialdepolarization)

Mem

bra

ne

po

ten

tial

(m

V)

Page 28: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Copyright © 2010 Pearson Education, Inc.

0 1 2 3 4

–70–55

0

+30

Mem

bra

ne

po

ten

tial

(m

V)

Time (ms)

Rel

ativ

e m

emb

ran

e p

erm

eab

ilit

y

Na+Na+

K+

K+

Outsidecell

Insidecell

Outsidecell

Insidecell

Depolarizing phase: Na+

channels open

Repolarizing phase: Na+

channels inactivating, K+

channels open

Action potential

PNa

PKThreshold

Na+

Na+

K+K+

Outside cell

Insidecell

Outsidecell

Insidecell

Inactivation gate

Activationgates

Potassiumchannel

Sodiumchannel

Resting state: All gated Na+

and K+ channels closed (Na+ activation gates closed; inactivation gates open)

Hyperpolarization: K+

channels remain open; Na+ channels resetting

2

2

3

4

4

1

11

3

Page 29: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

–70

+30

(a) Time = 0 ms (b) Time = 2 ms (c) Time = 4 ms

Voltageat 2 ms

Voltageat 4 ms

Voltageat 0 ms

Resting potential

Peak of action potential

Hyperpolarization

Me

mb

ran

e p

ote

nti

al

(mV

))

Page 30: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Time (ms)

Vo

ltag

eM

emb

ran

e p

ote

nti

al (

mV

)

–70

0

+30

Threshold

Actionpotentials

Stimulusamplitude

Page 31: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Stimulus

Mem

bra

ne

po

ten

tial

(m

V)

Time (ms)

–70

0

+30

0 1 2 3 4 5

Absolute refractoryperiod

Relative refractoryperiod

Depolarization(Na+ enters)

Repolarization(K+ leaves)

After-hyperpolarization

Page 32: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• Equilibrium Potentials (Cont’d)– The Nernst Equation

• Calculates the exact value of the equilibrium potential for each ion in mV

• Takes into consideration:– Charge of the ion– Temperature– Ratio of the external and internal ion concentrations

Page 33: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• The Distribution of Ions Across The Membrane

Page 34: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• The sodium-potassium pump– Enzyme - breaks down ATP when Na present– Calcium pump: Actively transports Ca2+ out of

cytosol

Page 35: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Na+ Na+

K+

K+

K+

K+

Na+

Na+

Na+

Na+

Cell interiorNa+

15 mMK+

150 mMCl–

10 mM A–

100 mMNa+

150 mMA–

0.2 mM

Cell exterior

K+

5 mM Cl–

120 mM

Cellexterior

Cellinterior

Plasmamembrane

Na+–K+

pumpDif

fusi

on

K+ N

a+ D

iffus

ion

-70 mV

Page 36: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Seymour Benzer – research leader in studies of Shaker Flies. In the 1970s, his lab was able to associate this mutant’s behavior to a gene that affects potassium channel development.

Page 37: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

Shaker Potassium Channels

Genetic approaches include screening for behavioral changes in animals with mutations in K+ channel genes. Such genetic methods allowed the genetic identification of the "Shaker" K+ channel gene in Drosophila before ion channel gene sequences were well known.

The Shaker (Sh) gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster. Under ether anesthesia, the fly’s legs will shake (hence the name); even when the fly is unanaesthetized, it will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan than regular flies; in their larvae, the repetitive firing of action potentials as well as prolonged exposure to neurotransmitters at neuromuscular junctions occurs.

The Sh gene plays a part in the operation of potassium ion channels, which are integral membrane proteins and are essential to the correct functioning of the cell.

Page 38: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

• Relative Ion Permeabilities of the Membrane at Rest – K+ channels: 4 subunits – Channel selectively permeable to K+

ions– MacKinnon—2003 Nobel Prize

• Mutations of specific K+ channels; Inherited neurological disorders

Page 39: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.
Page 40: Topic 3 The Neuronal Membrane at Rest Lange Biology 463 - Neurobiology.

END.