1 a, b, c, d all move solutes by diffusion down concentration gradient.

1

a, b, c, d all move solutes by diffusion down concentration gradient

2

Final mechanism can work against gradient e. Active transport

3


XXX XXXXX

X

4


XXX XXXXX

X

5


XXX XXXXX

X

Pump Protein

6


XXX XXXXX

X

7


XXX XXXXX

X

ATP

8


XXX XXXXX

X

ATP

ADP + Pi

9


XXX XXXXX

X

10


XXXXXXXXX

Concentrates against gradient

11

Ion pumps

Uniporter (one solute one way): I- pump in thyroid

Coupled transporters (two solutes) Symporter (same direction):Antiporter (opposite directions)

Na+/K+ ATPase in mitochondria

12

3. Cells can control solute distribution across their membranes by controlling:a. Synthesis of integral proteinsb. Activity of integral proteinsc. E supply for pumpsTherefore, expect that solutes would be unequally distributed across membranes

13

4. Actual ion distributionsSquid Axon (mM):ION [CYTOPLASM][ECF]Na+ 50 460K+ 400 10Cl- 40 540Ca++ <1 10A- 350 <1

Organic anions with multiple - chargesCOO- on proteins, sulfates, phosphates, etc....

14

5. Reasons for unequal distributiona. Metabolic production of organic anions A- produced by biosynthetic machinery

inside the cellb. Membrane permeability

impermeable to A- moderate Cl- permeability30-50X more permeable to K+ than

Na+

15

Given a and b, system passively comes to unequal ion distribution

Diffusion of ions governed not only by their concentration gradients, but also their electrical gradients

16

Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting

17

1 M sucrose


18

1 M sucrose


19

1 M sucrose 0.5 M sucrose

0.5 M sucrose


20

Permeable charged solutes will not come to concentration equilibrium across

membrane if other charged impermeable solutes are present

21

Na+

A-

Impermeable

22

Na+

A-

K+ Cl-

Permeable

23

Na+

A-

K+ Cl-

24

Na+

A-

K+ Cl-

25

Na+

A-K+

Cl-Na+

A-

K+ Cl-

26

Na+

A-K+

Cl-Na+

A-

K+ Cl-

At equilibrium: chemical force driving K+ out

27

Na+

A-K+

Cl-Na+

A-

K+ Cl-

At equilibrium: chemical force driving K+ out is exactly balanced by the electrical force

(electromotive force) holding K+ in

28

Na+

A-K+

Cl-Na+

A-

K+ Cl-


(electromotive force) holding K+ in Result: an unequal ion distribution which will

be maintained passively

29

Na+

A-K+

Cl-Na+

A-

K+ Cl-


(electromotive force) holding K+ in Result: an unequal ion distribution which will be

maintained passively“Donnan Equilibrium”

30

Donnan Equilibrium resembles situation in real cell, with one exception:cell is not maintained passively

Poison real cell and unequal distribution eventually goes away

31

c. Cells work via pumps to maintain unequal ion distribution

Na+ “leaks” in down chemical and electrical gradients

32

Na+

A-



33

Na+

A-



34

Na+

A-Na+Na+/K+ ATPase



35

Na+

A-

Na+



36

Na+

A-

Na+K+



37

Na+

A-

Na+

K+



38

If Na+ allowed to build up, inside becomes + , drives K+ out, and lose unequal distribution

Na+

A-

Na+

K+



39

Therefore, cells use combination of active and passive mechanisms to maintain unequal ion distributions REASON?

B. Membrane Potentials1. Significance of unequal distributionsWhenever an ion is unequally distributed

across a membrane, it endows the membrane with an electrical potential“membrane potential” (EM or VM)

40

2. Membrane potential measurementa. Voltmeter

41


42


43


44Inside is -80 mV


45

b. Calculate with Nernst equationEM = RT x ln[ion]outside

FZ ln[ion]inside

R = gas constant, T = abs. temperatureF = Faraday constant, Z = valance

Magnitude of the voltage due to 1 unequally distributed ion is directly proportional to the magnitude of its unequal distribution

46

BUT: can't use it for a real cellonly valid for 1 iononly valid for freely permeable ions

Can use it to calculate voltage due to any one freely permeable ion in a mixturee.g. K+ = -91 mV

Na+ = +65 mV

47

c. Alternative: GOLDMAN EQUATIONaccounts for multiple ionsaccounts for permeability of each multiplies [ion] ratios X permeability

constant for each ion, then sums up all to get total membrane EM

48

d. CONCLUSION: In ion mixture, each ion contributes to the overall EM in proportion to its permeability

Most permeable ions contribute the most charge

49

Which ion is most permeable? K+

real cell: inside is -80 mV = resting EM

cell is “negatively polarized”

50

EM is due almost exclusively to the unequal distribution of K+

Changes in [K+] alter EM easily

Changes in [Na+] do not alter EM

51

All cells have resting potential due to ion distributions

Some cells can use this electrical potential to transmit information

52

C. Nervous System Components1. Glial cells: supportive

diverse functions supportinsulationprotectioncommunication

up to 90% of nervous system by weight

53

2. Neuronssoma: nucleus, usual organellesdendrites: receptive, inputaxon: transmission (microm to m)axon terminals: synapse, output

54

55

3. Integrated Function of NeuronsGenerate and conduct electrical signals for communication or coordination

a. Propagation of electrical signals along individual cells (wires)

b. Communication of electrical information between cells

56

c. Model system for study: Squid giant axon (J.Z. Young)

57

c. Model system for study: Squid giant axon (J.Z. Young)

58

59

D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley

60


61


recording electrode

62


recording electrodecoupled with stimulating electrode

63



64Can change EM by adding charge



65Can change EM by adding charge

+++



66

STIMULUS

67

STIMULUSmV

68

STIMULUS

RESPONSE OF CELL

mV

69

STIMULUS

RESPONSE OF CELL

EM

(mV)

mV

0

70

STIMULUS

RESPONSE OF CELL

EM

(mV)

mV

0

71

EM

(mV)

mV

-80

0

72

EM

(mV)

mV

-80

Add negative charge, EM gets more negative0

73

EM

(mV)

mV

-80

HYPERPOLARIZATION


74

EM

(mV)

mV

-80EM moves away from 0 HYPERPOLARIZATION


75

EM

(mV)

mV

-80

0

76

EM

(mV)

mV

-80

0

77

EM

(mV)

mV

-80

Add positive charge, EM gets more positive0

78

EM

(mV)

mV

-80

Add positive charge, EM gets more positive

DEPOLARIZATION

0

79

EM

(mV)

mV

-80

Add positive charge, EM gets more positive

DEPOLARIZATION EM moves towards 0

0

80

EM

(mV)

mV

-80

0

81

EM

(mV)

mV

-80

0

82

EM

(mV)

mV

-80

0

83

EM

(mV)

mV

-80

0

84

2. Passive responsesa. Magnitude directly proportional to amount of current

Increase current: increase magnitude of passive depolarization

85

b. Magnitude inversely proportional to distance from stimulus

Die out locally

86


Die out locally

87


Die out locally

88


Die out locally

89


Die out locally

90


Die out locally

91

EM

(mV)

mV

-80

0

92

EM

(mV)

mV

-80

0

93

3. At some point, small increase in applied current triggers a membrane depolarization much greater than the stimulus currentActive responseACTION POTENTIAL

94

Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement

95


96


97


98


99


100


101


102

4. Voltage changes during action potentials

103


EM

Time (msecs)

mVolts

104


0-20-40-60-80

EM

Time (msecs)

mVolts

105


EM

Time (msecs)0 1 2 3 4

mVolts

0-20-40-60-80

106


EM


mVolts

1. Resting membrane before arrival

1

0-20-40-60-80

107


EM


mVolts

2. Depolarization to 0 mV

1

20

-20-40-60-80

108


EM


mVolts

2. Depolarization to 0 mV hyperpolarizing overshoot

1

20

-20-40-60-80

109


EM


mVolts

3. Repolarization back to -80 mV

1

2 30

-20-40-60-80

110


EM


mVolts

4. Hyperpolarizing afterpotential

1

2 3

4

0-20-40-60-80

111


EM


mVolts

5. Return to resting

1

2 3

4 5

0-20-40-60-80

1 a, b, c, d all move solutes by diffusion down concentration gradient.

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