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

2 Final mechanism can work against gradient e. Active transport

3 Final mechanism can work against gradient e. Active transport XXX XX XXX X

4 Final mechanism can work against gradient e. Active transport XXX XX XXX X

5 Final mechanism can work against gradient e. Active transport XXX XX XXX X Pump Protein

6 Final mechanism can work against gradient e. Active transport XXX XX XXX X

7 Final mechanism can work against gradient e. Active transport XXX XX XXX X ATP

8 Final mechanism can work against gradient e. Active transport XXX XX XXX X ATP ADP + P i

9 Final mechanism can work against gradient e. Active transport XXX XX XXX X

10 Final mechanism can work against gradient e. Active transport XXX 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 proteins b. Activity of integral proteins c. E supply for pumps Therefore, expect that solutes would be unequally distributed across membranes

13 4. Actual ion distributions Squid Axon (mM): ION[CYTOPLASM][ECF] Na K Cl Ca ++ <110 A - 350<1 Organic anions with multiple - charges COO - on proteins, sulfates, phosphates, etc....

14 5. Reasons for unequal distribution a. Metabolic production of organic anions A - produced by biosynthetic machinery inside the cell b. Membrane permeability impermeable to A - moderate Cl - permeability 30-50X 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 Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting

18 1 M sucrose Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting

19 1 M sucrose 0.5 M sucrose Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting

20 Permeable charged solutes will not come to concentration equilibrium across membrane if other charged impermeable solutes are present

21 Na + A-A- Impermeable

22 Na + A-A- K+K+ Cl - Permeable

23 Na + A-A- K+K+ Cl -

24 Na + A-A- K+K+ Cl -

25 Na + A-A- K+K+ Cl - Na + A-A- K+K+ Cl -

26 Na + A-A- K+K+ Cl - Na + A-A- K+K+ Cl - At equilibrium: chemical force driving K + out

27 Na + A-A- K+K+ Cl - Na + A-A- K+K+ Cl - At equilibrium: chemical force driving K + out is exactly balanced by the electrical force (electromotive force) holding K + in

28 Na + A-A- K+K+ Cl - Na + A-A- K+K+ Cl - At equilibrium: chemical force driving K + out is exactly balanced by the electrical force (electromotive force) holding K + in Result: an unequal ion distribution which will be maintained passively

29 Na + A-A- K+K+ Cl - Na + A-A- K+K+ Cl - At equilibrium: chemical force driving K + out is exactly balanced by the electrical force (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-A- c. Cells work via pumps to maintain unequal ion distribution Na + “leaks” in down chemical and electrical gradients

33 Na + A-A- c. Cells work via pumps to maintain unequal ion distribution Na + “leaks” in down chemical and electrical gradients

34 Na + A-A- Na + /K + ATPase c. Cells work via pumps to maintain unequal ion distribution Na + “leaks” in down chemical and electrical gradients

35 Na + A-A- c. Cells work via pumps to maintain unequal ion distribution Na + “leaks” in down chemical and electrical gradients

36 Na + A-A- K+K+ c. Cells work via pumps to maintain unequal ion distribution Na + “leaks” in down chemical and electrical gradients

37 Na + A-A- K+K+ c. Cells work via pumps to maintain unequal ion distribution Na + “leaks” in down chemical and electrical gradients

38 If Na + allowed to build up, inside becomes +, drives K + out, and lose unequal distribution Na + A-A- K+K+ c. Cells work via pumps to maintain unequal ion distribution Na + “leaks” in down chemical and electrical gradients

39 Therefore, cells use combination of active and passive mechanisms to maintain unequal ion distributions REASON? B. Membrane Potentials 1. Significance of unequal distributions Whenever an ion is unequally distributed across a membrane, it endows the membrane with an electrical potential “membrane potential” (E M or V M )

40 2. Membrane potential measurement a. Voltmeter

41 2. Membrane potential measurement a. Voltmeter

42 2. Membrane potential measurement a. Voltmeter

43 2. Membrane potential measurement a. Voltmeter

44 Inside is -80 mV 2. Membrane potential measurement a. Voltmeter

45 b. Calculate with Nernst equation E M =RT x ln[ion] outside FZln[ion] inside R = gas constant, T = abs. temperature F = 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 cell only valid for 1 ion only valid for freely permeable ions Can use it to calculate voltage due to any one freely permeable ion in a mixture e.g. K + = -91 mV Na + = +65 mV

47 c. Alternative: GOLDMAN EQUATION accounts for multiple ions accounts for permeability of each multiplies [ion] ratios X permeability constant for each ion, then sums up all to get total membrane E M

48 d. CONCLUSION: In ion mixture, each ion contributes to the overall E M in proportion to its permeability Most permeable ions contribute the most charge

49 Which ion is most permeable? K+K+ real cell: inside is -80 mV = resting E M cell is “negatively polarized”

50 E M is due almost exclusively to the unequal distribution of K + Changes in [K + ] alter E M easily Changes in [Na + ] do not alter E M

51 All cells have resting potential due to ion distributions Some cells can use this electrical potential to transmit information

52 C. Nervous System Components 1. Glial cells: supportive diverse functions support insulation protection communication up to 90% of nervous system by weight

53 2. Neurons soma: nucleus, usual organelles dendrites: receptive, input axon: transmission (microm to m) axon terminals: synapse, output

54

55 3. Integrated Function of Neurons Generate 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 Neurons 1. Intracelluar Recording:Hodgkin and Huxley

60 D. Electrical Characteristics of Neurons 1. Intracelluar Recording:Hodgkin and Huxley

61 D. Electrical Characteristics of Neurons 1. Intracelluar Recording:Hodgkin and Huxley recording electrode

62 D. Electrical Characteristics of Neurons 1. Intracelluar Recording:Hodgkin and Huxley recording electrode coupled with stimulating electrode

63 D. Electrical Characteristics of Neurons 1. Intracelluar Recording:Hodgkin and Huxley recording electrode coupled with stimulating electrode

64 Can change E M by adding charge D. Electrical Characteristics of Neurons 1. Intracelluar Recording:Hodgkin and Huxley recording electrode coupled with stimulating electrode

65 Can change E M by adding charge +++ D. Electrical Characteristics of Neurons 1. Intracelluar Recording:Hodgkin and Huxley recording electrode coupled with stimulating electrode

66 STIMULUS

67 STIMULUS mV

68 STIMULUS RESPONSE OF CELL mV

69 STIMULUS RESPONSE OF CELL E M (mV) mV 0

70 STIMULUS RESPONSE OF CELL E M (mV) mV 0

71 E M (mV) mV -80 0

72 E M (mV) mV -80 Add negative charge, E M gets more negative 0

73 E M (mV) mV -80 HYPERPOLARIZATION Add negative charge, E M gets more negative 0

74 E M (mV) mV -80 E M moves away from 0 HYPERPOLARIZATION Add negative charge, E M gets more negative 0

75 E M (mV) mV -80 0

76 E M (mV) mV -80 0

77 E M (mV) mV -80 Add positive charge, E M gets more positive 0

78 E M (mV) mV -80 Add positive charge, E M gets more positive DEPOLARIZATION 0

79 E M (mV) mV -80 Add positive charge, E M gets more positive DEPOLARIZATION E M moves towards 0 0

80 E M (mV) mV -80 0

81 E M (mV) mV -80 0

82 E M (mV) mV -80 0

83 E M (mV) mV -80 0

84 2. Passive responses a. 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 b. Magnitude inversely proportional to distance from stimulus Die out locally

87 b. Magnitude inversely proportional to distance from stimulus Die out locally

88 b. Magnitude inversely proportional to distance from stimulus Die out locally

89 b. Magnitude inversely proportional to distance from stimulus Die out locally

90 b. Magnitude inversely proportional to distance from stimulus Die out locally

91 E M (mV) mV -80 0

92 E M (mV) mV -80 0

93 3. At some point, small increase in applied current triggers a membrane depolarization much greater than the stimulus current Active response ACTION POTENTIAL

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

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

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

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

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

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

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

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

Voltage changes during action potentials

Voltage changes during action potentials EMEM Time (msecs) mVolts

Voltage changes during action potentials EMEM Time (msecs) mVolts

Voltage changes during action potentials EMEM Time (msecs) mVolts

Voltage changes during action potentials EMEM Time (msecs) mVolts 1. Resting membrane before arrival

Voltage changes during action potentials EMEM Time (msecs) mVolts 2. Depolarization to 0 mV

Voltage changes during action potentials EMEM Time (msecs) mVolts 2. Depolarization to 0 mV hyperpolarizing overshoot

Voltage changes during action potentials EMEM Time (msecs) mVolts 3. Repolarization back to -80 mV

Voltage changes during action potentials EMEM Time (msecs) mVolts 4. Hyperpolarizing afterpotential

Voltage changes during action potentials EMEM Time (msecs) mVolts 5. Return to resting