פיזיולוגיה הרצאה א - 14-02-2011

8/6/2019 פיזיולוגיה הרצאה א - 14-02-2011

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mailto:[email protected]






Nutrition and Neuroscience

" - ". . .Christiaan Eijkman Nobel Lecture Nobelprize org 13 Feb 2011

:// . / / / / / -http nobelprize org nobel_prizes medicine laureates 1929 eijkman.lecture html

o b e l P r i z e i n P h y s i o l o g y o r M e d i c i n e 1 9 2 9

h ris ti aa n E ij km an“ ”For his discovery of Anti Neuritic Vitamin

ir Frederick Gowland Hopkins“ -For his discovery of the growth stimulating vitam



Nobel Prizes in NutritionScience

Nobel Prize in ChemistrySynthesis of Vitamins

Walter Norman Haworth (1937) Vitamin C

Paul Karrer (1937) Vitamin E

Robert Burns Woodward (1965)* Vitamin B 12

Structure of Vitamins

Paul Karrer (1937) Vitamin A and B

Richard Kuhn (1938) Vitamin B 2

Lord (Alexander R.) Todd (1957)*

Vitamin B 12

Dorothy Crowfoot Hodgkin (1964)*

Vitamin B 12

Nobel Prize in Physiology or MedicineDiscovery of Vitamins

Christiaan Eijkman (1929)

Vitamin B 1

Sir Frederick Gowland Hopkins (1929) Growth Stimulating Vitamins

George Hoyt Whipple (1934)*

Vitamin B 12George Richards Minot (1934)*

Vitamin B 12William Parry Murphy (1934)*

Vitamin B 12

Henrik Carl Peter Dam (1943) Vitamin K

Isolation of Vitamins

Adolf Otto Reinhold Windaus (1928)* Vitamin D

Albert von Szent-Györgyi Nagyrapolt(1937)

Vitamin C

Richard Kuhn (1938) Vitamin B 2 and B 6

Edward Adelbert Doisy (1943)

Vitamin K

" ". . .The Nobel Prize and the Discovery of Vitamins Nobelprize org 13 Feb 2011:// . / / / / / .http nobelprize org nobel_prizes medicine articles carpenter index html

( )obel Peace Prize 1949 - ( )Lord John Boyd Orr of Brechin, ; , ; )ntist MD Director of Rowett Institute Scotland Director General of UN FAO

http://nobelprize.org/nobel_prizes/chemistry/laureates/1937/index.html










http://nobelprize.org/nobel_prizes/medicine/laureates/1929/index.html



































The Human Brain

• ~100 Million Neurons, ~ 1000

million cells• 2% Body Weight• 15% Cardiac Output• 20-30% Resting Metabolic Rate• No Stora e Tissue



Nerve Cells



Outline

• Membrane Potential• Resting Potential• The Nerve Cell• Action Potentials• Glial Cells• Central Nervous System

• Autonomic Nervous System – Sympathetic – Parasympathetic



Cell Membranes and Transporters

+ ++ + +

--

-

++

+

+ +- - - -



The cell membrane

• Diffusion• Osmosis

• Passive Transprt• Active Transport• The ionic basis of membrane

potential



E xcita b le M e m b ra n e s

• Resting potential• Presynaptic potential – depolarization

and hyperpolarization• Ion Channels• Propagating action potentials



Transport across cellmembranes

X+ X+

in out

• Simple diffusion• Facilitated Diffusion• Primary Active Transport• Co-transport• Counter-transport• (Endocytosis)

GRADIENT



Simple Diffusion

GR A D I E N T



Simple Diffusion Permeable membrane

J ( / )mmolsec = P ( / )cmsec A (cm2) (CA- CB) ( / )mmolL = ; = ; = ; =J net rate of diffusion P permeability A surface area for diffusion C concentration



Facilitated Diffusion–Semi permeable selective membranet 0



Facilitated Diffusion–Semi permeable selective membranet ∞



Diffusion

Transport

Rate

Concentration

S i m p l

e d i f f u s

i o n

- Carrier mediated transport T m



Osmosis Semi permeable membranet 0



Osmosis Semi permeable membranet ∞



Osmosis Semi permeable membrane

π (atm) = g (Osm/mol) C(mmol/L) σ (0-1) RTπ

= ; = / ; = ;osmotic pressure g N particles mol solution C concentration σ

=reflection coefficie

= ( . - / - ); =R gas constant 0 82 L atm mol K T absolute temperature K



Tonicity / Osmolarity[ ] = /Urea 2 mol L[ ] = /NaCl 1 mol L

+

- -

+-

+








+

- -

+-

+

s m o l a r i t y = ( / ) g number particles mol C ( / ) concentration mol L

: / = /NaCl 2 x 1 mol L 2 Osm L: / = /Urea 1 x 2 mol L 2 Osm L

Solutions are i s o s m o t i c








To n i c i t y = π (atm) = g (Osm/mol) C(mmol/L) σ (0-1) RT

RT 37⁰C = .25 45 L • /atmmolσ NaCl : .0 3 π NaCl = 2 x 1 mol/L x 0.3 = RT = 0.6RT = 15.3 atmσ Urea : .0 05 π Urea = 1 x 2 mol/L x 0.05 = RT = 0.1RT = 2.5 atm! Solutions are o t i s o t o n i c

π

+

- -

+-

+



Tonicity / Osmolarity[ ] = /Urea 2 mol L H y p o t o n i c[ ] = /NaCl 1 mol L H y p e r t o n i c

To n i c i t y = π (atm) = g (Osm/mol) C(mmol/L) σ (0-1) RT

RT 37⁰C = .25 45 L • /atmmolσ NaCl : .0 3 π NaCl = 2 x 1 mol/L x 0.3 = RT = 0.6RT = 15.3 atmσ Urea : .0 05 π Urea = 1 x 2 mol/L x 0.05 = RT = 0.1RT = 2.5 atm! Solutions are o t i s o t o n i c

π H20

+

- -

+-

+



Electrogenic Transport–Semi permeable selective membrane

+

-

+- +

+

-

+- +



Membrane Potential–Selective membrane permeable to K +, impermeable to Cl -

+- +

- +-

+

-

+-

+-

+-

+-

-V+

0

[K+Cl -] in >

[K+Cl -] out Concentration gradient

t 0



Membrane Potential–Selective membrane permeable to K +, impermeable to Cl -

+-

+

-+ -

+-

+ -

+

-

+ -

+

-

-V+

0

[K+][Cl -] in > [K+][Cl -] out

Concentration gradient

=

( )Potential voltage gradien

t ∞



Active Transport: Na+/K+ATPase

Na

Na

Na

Na+

K+

K+

Na+

Na+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+



Na+/K+ ATPase

Na

Na

Na

ATP

Na+

K+

K+

Na+

Na+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+



Na+/K+ ATPase

Na

ADP

P

Na+

K+

K+

Na+

Na+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+



Na+/K+ ATPase

Na

Na+

K+

K+

Na+

Na+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+

Na+

Na+

ADP

P



Na+/K+ ATPase

Na

K+

K+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+

Na+

Na+

K+

K+

P



Na+/K+ ATPase

Na

K+

K+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+

Na+

Na+

P



Na+/K+ ATPase

K+

K +

K+

K+

K+

K+

K +

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+

Na+

Na+

Pi



Na+/K+ ATPase

K++

K+

K+

K+

K+K +

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+

Na+

Na+

Pi

K +

K +

K +



Na+/K+ ATPase

K++

K+

K+

K+

K+K +

K+

K+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

Na+

K+

Na+

Na+

Pi

K +

K +

K +



Na+/K+ ATPase

E

-E P -E P

-E PATP

+ADP Pi

3Na+in 3Na+out

2K+out2K

+in



Transport across cellmembranes

Simple diffusion +Na+Na

+K

K+

+ + + + + + +

- - - - - - - -

- ( )Co transport Symport

+Na

GlucoseGlucose

Facilitated Diffusio

CO2

02

Cl -

Cl -



Electrochemical Equillibrium

X+ X+

)(][][

ln)X)X)X out in

out

in

out in E E zF X

X

RT −+=(−(=(∆ +

+

+++

µ µ µ

in out

Concentration gradient

=

( )Potential voltage gradien



Equilibrium Potential

s t Equation : E x= - . / (2 3 RT zF log 10 [ ]X in /[ ]XE = equilibrium potential ( )mV. / =2 3RT F constant (~ 60 mV at 37 ⁰ )C=Z charge on the ion (+1 for Na + & K+; - 1 for Cl -; + 2

for Ca +2 .)etc

Membrane Potential( )oldman Hodgkin Katz GHK Equat ion :

iCaiCli NaiK

oCaoClo NaoK 10m [Ca] p[Cl] p[Na] p[K] p

[Ca] p[Cl] p[Na] p[K] plog60V

+++

+++=

=P permeability to ion current



Normal High PotassiumIon Extracellular Intracellular Extracellular Intracellular Na+ 117 30 114 29K+ 3 90 6 91Cl- 120 4 120 7.9A- 0 116 0 112.1Relative Volume 1 1.035Equillibrium potential z E xNa+ 1 35 1 36K+ 1 -89 1 -71Cl- -1 -89 -1 -71A-Membrane Potential -85 mV -68 mV

Normal Low ChlorideIon Extracellular Intracellular Extracellular Intracellular Na+ 117 30 117 30.5K+ 3 90 3 89.5Cl- 120 4 60 2A- 0 116 60 118Relative Volume 1 0.98Equillibrium potential z E xNa+ 1 35 1 35K+ 1 -89 1 -88Cl- -1 -89 -1 -89A-Membrane Potential -85 mV -85 mV



Nerve Cells



Nerve Cell Anatomy







Recording Nerve Activity

, .Stuart GJ Sakmann B Active propagation of somatic action potentials into neocortical

.pyramidal cell dendrites. ; ( ): - . : .Nature 1994 Jan 6 367 6458 69 72 PMID 8107777

-V+

0

+ + ---- - + + ++ + +- - ++++- - - - -- - - - -

-85 mV

Vm

t imestimulus

h f



Characteristics of ActionPotentials

Stereotypical size and shapePropagationAll-or-none responseVm ( )V

( )Time msec

-70

-90

0

+35

Stimulus



Action Potentials

DepolarizationHyperpolarizationInward CurrentOutward Current

Threshold

OvershootUndershoot (hyperpolarizingafterpotential)

Refractory period

V m (mV)

-70

-90

0

+35

Stimulus

i b i f h i



Ionic basis of the ActionPotential

1.Resting membrane potential2.Upstroke of the action potential3.Repolarization4.Hyperpolarizing afterpotential

These steps are mediated by thecollective action of specializedchannels acting together

The action potential is the summedmembrane potential of ion fluxes

enerated b all of the channels



Gated Channels

igand Gated oltage Gated

- - -

+ + +

Rest



Gate Channels


- - - + +

+ + +

( )Upstroke sub threshold

+Na



Gated Channels


++++

- - - - -

( )Upstroke breakthrough threshold

+Na



Gated Channels


++ - -

- - + +

( )Upstroke breakthrough threshold

+Na

+K



Gated Channels


- - - -

+ ++ +

+Repolarization overshoot

+K



Gated Channels


- - -

+ + +

Rest





G ti f th A ti P t ti l



potentialin

millivolts

0

-70resting state

Na + gate

opening

K+ gate

opening

Na + /K+ pump

operating

Action Potential

The action potential ispropagated down thelength of a nerve cell.

time

Generation of the Action Potential

intracellular environment of thenerve

cellmembrane

cellmembrane

[Na +] [K+]

This ion inbalance is maintained by the Na +-K+ ATPase pump.

The intracellular side of the membrane is ~70mv lower inpotential that the extracellular side.

-70mv

extracellular environment

e fr ac to ry Pe ri od



V m (mV)

-70

-

0

+35

Equilibrium potential

Equilibrium potential

Resting Membranepotential

e fr ac to ry Pe ri od AbsoluteRelative

+Inward Na Current

+Outward K Current

.0 .0

+65



Myelinated Axons

• Oligodendrocytes and Schwann cells• Saltatory nerve conduction• Spinal Cord Injury• Demyelinating neuropathy•







myelinated nerve cell (Schwann cell)







Schwanncell

unmyelinated nerve cell

myelinated nerve cell

Schwann cells in the CNS

Oligodendrocite cells in the PNS

saltatory conductancenode to node

node of Ranvier



The Synapse

• A junction between cells allowingtransmission of information carriedby action potential

• Electrical and chemical synapses• Nerve – Nerve; Neuromuscular

synapes, etc.

• Presynaptic potential• Excitatory post synaptic potential• Inhibitory post synaptic potential







AP

axon

synaptic vesicles

presynaptic membrane

postsynaptic membranesynapse

postsynaptic receptors direct ion channels

Action Potentials Code



Action Potentials CodeInformation

Nerve

Receptor

Stimulus

ha si c Recep tor( )a pid ly a da pti ng

onic Receptor( )lowly adapting



A Simple Reflex

• Knee jerk, pain – Simple stereotypical response – Does not require central processing

– Integrates external stimuli andappropriate response

• How does this give rise to more

complex phenomena?



Sensory Input

Motor Output

Summation

Information



Documents

פיזיולוגיה הרצאה א - 14-02-2011