1. Fundamentals of the Nervous System and Nervous Tissue11
P A R T B
Fundamentals of the Nervous System and Nervous Tissue

2. Neurophysiology 1: Channels, Gates, & Gradients

3. Action potentials, or nerve impulses, are:
Neurophysiology
Neurons are highly irritable / excitable / able to rapidly change their voltage
Action potentials, or nerve impulses, are:
Electrical impulses carried along the length of axons
Always the same regardless of stimulus (“all or none phenomena” – no such thing as big or small a.p.s)
The first functional feature of the nervous system (the second is synaptic transmission)
See

4. Electricity Definitions
Voltage (V) – measure of potential energy generated by separated charge
Potential difference – voltage measured between two points
Current (I) – the flow of electrical charge between two points
Resistance (R) – hindrance to charge flow
Insulator – substance with high electrical resistance
Conductor – substance with low electrical resistance

5. Electrical Current and the Body
Reflects the flow of ions rather than electrons
There is a potential on either side of membranes when:
The number of ions is different across the membrane
The membrane provides a resistance to ion flow

6. Types of plasma membrane ion channels:
Role of Ion Channels
Types of plasma membrane ion channels:
Passive, or leakage, channels – always open
Active channels or gates – usually closed, open when signaled
Chemically gated channels – open with binding of a specific neurotransmitter
Voltage-gated channels – open and close in response to changes in the membrane potential
Mechanically gated channels – open and close in response to physical deformation of receptors

7. Operation of a Chemically-Gated Channel
Example: Na+-K+ gated channel
Closed when a neurotransmitter is not bound to the extracellular receptor
Na+ cannot enter the cell and K+ cannot exit the cell
Open when a neurotransmitter is attached to the receptor
Na+ enters the cell and K+ exits the cell

8. Operation of a Gated Channel
Figure 11.6a

9. Operation of a Voltage-Gated Channel
Example: Na+ channel
Closed when the intracellular environment is negative
Na+ cannot enter the cell
Open when the intracellular environment is positive
Na+ can enter the cell

10. Operation of a Voltage-Gated Channel
Figure 11.6b

11. When gated channels are open:
Ions move quickly across the membrane
Movement is along their electrochemical gradients
An electrical current is created
Voltage changes across the membrane

12. Electrochemical Gradient
Ions flow along their chemical gradient when they move from an area of high concentration to an area of low concentration
Ions flow along their electrical gradient when they move toward an area of opposite charge
Electrochemical gradient – the electrical and chemical gradients taken together

13. Electrochemical Gradients in NeuronsK+
Na+
Proteins -

14. Electrochemical Gradients in Neurons
Sodium
Potassium
Intracellular Concentration
Extracellular Concentration
Chemical Gradient
Electrical Gradient
Combined
Electrochemical Gradient
Movement During
Action Potential

15. Electrochemical Gradients in Neurons
Sodium
Potassium
Intracellular Concentration
Low
High
Extracellular Concentration
Chemical Gradient
Attracted Inward
(Diffusion)
Attracted Outward
Electrical Gradient
(Since cell is -70 mV and Na is positive)
(Since cell is -70 mV and K is positive)
Combined
Electrochemical Gradient
Strongly Attracted Inward
Movement During
Action Potential
Flows Rapidly Into Cell
Flows Slowly
Out of Cell

16. Neurophysiology 2: Electrical Events in Neurons

17. Resting Membrane Potential (Vr)
The potential difference (–70 mV) across the membrane of a resting neuron
It is generated by different concentrations of Na+, K+, Cl, and protein anions (A)
Ionic differences are the consequence of:
Differential permeability of the neurilemma to Na+ and K+
Operation of the sodium-potassium pump using energy from splitting ATP to move Na+ and K+ against their concentration gradients (3 Na+ pumped out and 2 K+ pumped in for each ATP molecule)

18. Measuring Mebrane Potential
Figure 11.7

19. Resting Membrane Potential (Vr)
ATP
Figure 11.8

20. Three Voltage Potentials
Resting Potentials: Neurons are waiting to receive a signal
Graded Potentials: Neurons have received one or more signals, and are combining their voltages (the signals can be either excitatory or inhibitory, and they vary in their size = “graded”)
Action Potentials: Neurons are sending a signal after receiving enough excitatory input

21. Resting Potential
Neurons at rest have a voltage potential of approx. -70 mV (inside the cell)
RP results from combination of electrical forces and chemical forces acting on Na+, K+, Cl-, and various anions
Passive channels allow a few ions to cross the membrane randomly
Active gates are closed

22. Membrane Potentials: Signals
Used to integrate, send, and receive information
Membrane potential changes are produced by:
Changes in membrane permeability to ions
Alterations of ion concentrations across the membrane
Types of signals – graded potentials and action potentials

23. Changes in Membrane Potential
Changes are caused by three events
Depolarization – the inside of the membrane becomes less negative
Repolarization – the membrane returns to its resting membrane potential
Hyperpolarization – the inside of the membrane becomes more negative than the resting potential

24. Changes in Membrane Potential
Figure 11.9

25. Graded Potentials
Short-lived, local changes in membrane potential
Decrease in intensity with distance
Magnitude varies directly with the strength of the stimulus
Sufficiently strong graded potentials can initiate action potentials

26. Graded Potentials
Figure 11.10

27. Graded Potentials
Voltage changes are decremental
Current is quickly dissipated due to the leaky plasma membrane
Only travel over short distances

28. Graded Potentials
Figure 11.11

29. Graded Potentials
Voltage changes that vary in size are called graded potentials
They are temporary, occur at synapses (on the post-synaptic membrane), vary in size according to the strength of the stimulus, and spread in all directions along the membrane for short distances (they get weaker farther from the synapse, and the distance they spread depends on the stimulus strength)
There are two kinds: EPSPs and IPSPs

30. Postsynaptic Potentials
Neurotransmitter receptors mediate changes in membrane potential according to:
The amount of neurotransmitter released
The amount of time the neurotransmitter is bound to receptors
The two types of postsynaptic potentials are:
EPSP – excitatory postsynaptic potentials
IPSP – inhibitory postsynaptic potentials
PLAY
InterActive Physiology ®:
Nervous System II: Synaptic Transmission, pages 7–12

31. Excitatory Post-Synaptic Potentials (EPSPs)
EPSPs occur when a synapse sends a signal for the next neuron to fire an AP
EPSPs depolarize the membrane slightly by opening chemical gates for sodium
If the membrane is depolarized enough, the post-synaptic neuron will fire an AP
The amount of depolarization required for an AP is called the threshold – usually around -50 to -55mV

32. Excitatory Postsynaptic Potentials
EPSPs are graded potentials that can initiate an action potential in an axon
Use only chemically gated channels
Na+ and K+ flow in opposite directions at the same time
Postsynaptic membranes do not generate action potentials

33. Excitatory Postsynaptic Potential (EPSP)
Figure 11.19a

34. Inhibitory Post-Synaptic Potentials (IPSPs)
IPSPs occur when a synapse sends a signal for the next neuron NOT to fire an AP
IPSPs hyperpolarize the membrane slightly by opening chemical gates for chlorine (Cl- enters cell)

35. Inhibitory Synapses and IPSPs
Neurotransmitter binding to a receptor at inhibitory synapses:
Causes the membrane to become more permeable to potassium and chloride ions
Leaves the charge on the inner surface negative
Reduces the postsynaptic neuron’s ability to produce an action potential

36. Inhibitory Postsynaptic (IPSP)
Figure 11.19b

37. Changes in Membrane Potential
EPSP!!!
IPSP!!!
EPSP or IPSP??
Figure 11.9

38. Integration of Graded Potentials
EPSPs add together, while IPSPs subtract – so the voltage around synapses is always rising and falling slightly (it is depolarizing and hyperpolarizing)
If the overall voltage reaches threshold at the axon hillock, the neuron fires an AP
This combination, or integration, of EPSPs & IPSPs is how neurons make decisions

39. Summation
A single EPSP cannot induce an action potential
EPSPs must summate temporally or spatially to induce an action potential
Temporal summation – presynaptic neurons transmit impulses in rapid-fire order

40. IPSPs can also summate with EPSPs, canceling each other out
Summation
Spatial summation – postsynaptic neuron is stimulated by a large number of terminals at the same time
IPSPs can also summate with EPSPs, canceling each other out
PLAY
InterActive Physiology ®:
Nervous System II: Synaptic Potentials

41. Summation
Figure 11.20

42. Neurophys 3: Action Potentials

43. The Role of Action Potentials
APs are the electrical component of neuronal communication (synaptic transmission is the chemical component)
APs send an electrical signal from the cell body of one neuron, down its axon, and to its axon terminals, where the electrical signal is converted into a chemical signal by the process of synaptic transmission

44. AP Characteristics
All-or-None Phenomena (once they start, they keep going – and they are always the same size)
Propogate in one direction only – from axon hillock to axon terminal
Consist of a quick depolarization followed by a repolarization – then a hyperpolarization before the neuron recovers to the RP
Since stimulus intensity is not coded by AP size, it must be coded by AP frequency (more APs indicate a larger stimulus)

45. Structure of Na+ Gates
Na+ gates have two mechanisms that close them, so we say that the gate is closed, open, or inactivated
These are voltage-activated gates, opening when the membrane is depolarized to threshold
Closed
Open
Inactivated

46. Action of Na+ Gates During the AP
Closed during RP
Open when membrane reaches threshold, allowing Na+ to enter cell, resulting in rising phase of AP
Inactivated when the AP reaches its peak
Reset to closed state during hyperpolarization

47. Action of K+ Gates During the AP
Simpler gate than Na+, since it is either open or closed – also voltage activated
Closed during RP
Open more slowly than Na+ gate, about the time when the AP reaches its peak
Allow K+ ions to exit the cell, repolarizing the membrane and resulting in the falling phase of the AP
Stay open longer than Na+ gate, resulting in hyperpolarization when the voltage overshoots the RP

48. 1: Resting Potential

49. 2:
Rising Phase

50. 3:
Falling Phase

51. 4:
Overshoot

52. Summary of Gate Actions during APs
Sodium Gate
Potassium Gate
Resting Potential
Rising Phase
Falling Phase
Overshoot

53. Summary of Gate Actions during APs
Sodium Gate
Potassium Gate
Resting Potential
Closed
Rising Phase
Open
Falling Phase
Inactivated
Overshoot

54. Refractory Periods
After a neuron has fired an AP, it is unable to fire again until the refractory period has passed
Two types: absolute refractory period and relative refractory period

55. Absolute Refractory Period
The neuron is completely unable to send another AP during this time, no matter how intense the stimulus
Occurs during rising phase and part of falling phase
Since Na+ gates are already open, neuron can’t send another signal
The absolute refractory period serves to:
Ensure that each action potential is separate
Enforce one-way transmission of nerve impulses

56. Relative Refractory Period
The neuron is usually unable to send another AP during this time, but if the stimulus is strong enough, it will fire again
Occurs during end of falling phase and overshoot
Na+ gates are closed, but K+ are open – so the stimulus must be very strong to reach threshold again

57. Absolute and Relative Refractory Periods
Figure 11.15

58. Action Potentials (APs)
A brief reversal of membrane potential with a total amplitude of 100 mV
Action potentials are only generated by muscle cells and neurons
They do not decrease in strength over distance
They are the principal means of neural communication
An action potential in the axon of a neuron is a nerve impulse
PLAY
InterActive Physiology ®:
Nervous System I: The Action Potential

59. Action Potential: Resting State
Na+ and K+ channels are closed
Leakage accounts for small movements of Na+ and K+
Each Na+ channel has two voltage-regulated gates
Activation gates – closed in the resting state
Inactivation gates – open in the resting state
Figure

60. Action Potential: Depolarization Phase
Na+ permeability increases; membrane potential reverses
Na+ gates are opened; K+ gates are closed
Threshold – a critical level of depolarization (-55 to -50 mV)
At threshold, depolarization becomes self-generating
Figure

61. Action Potential: Repolarization Phase
Sodium inactivation gates close
Membrane permeability to Na+ declines to resting levels
As sodium gates close, voltage-sensitive K+ gates open
K+ exits the cell and internal negativity of the resting neuron is restored
Figure

62. Action Potential: Hyperpolarization
Potassium gates remain open, causing an excessive efflux of K+
This efflux causes hyperpolarization of the membrane (undershoot)
The neuron is insensitive to stimulus and depolarization during this time
Figure

63. Action Potential: Role of the Sodium-Potassium Pump
Repolarization
Restores the resting electrical conditions of the neuron
Does not restore the resting ionic conditions
Ionic redistribution back to resting conditions is restored by the sodium-potassium pump

64. Phases of the Action Potential
1 – resting state
2 – depolarization phase
3 – repolarization phase
4 – hyperpolarization
Figure 11.12

65. Propagation of an Action Potential (Time = 0ms)
Na+ influx causes a patch of the axonal membrane to depolarize
Positive ions in the axoplasm move toward the polarized (negative) portion of the membrane
Sodium gates are shown as closing, open, or closed

66. Propagation of an Action Potential (Time = 0ms)
Figure 11.13a

67. Propagation of an Action Potential (Time = 2ms)
Ions of the extracellular fluid move toward the area of greatest negative charge
A current is created that depolarizes the adjacent membrane in a forward direction
The impulse propagates away from its point of origin

68. Propagation of an Action Potential (Time = 2ms)
Figure 11.13b

69. Propagation of an Action Potential (Time = 4ms)
The action potential moves away from the stimulus
Where sodium gates are closing, potassium gates are open and create a current flow

70. Propagation of an Action Potential (Time = 4ms)
Figure 11.13c

71. Threshold and Action Potentials
Threshold – membrane is depolarized by 15 to 20 mV
Established by the total amount of current flowing through the membrane
Weak (subthreshold) stimuli are not relayed into action potentials
Strong (threshold) stimuli are relayed into action potentials
All-or-none phenomenon – action potentials either happen completely, or not at all

72. Coding for Stimulus Intensity
All action potentials are alike and are independent of stimulus intensity
Strong stimuli can generate an action potential more often than weaker stimuli
The CNS determines stimulus intensity by the frequency of impulse transmission

73. Stimulus Strength and AP Frequency
Figure 11.14

74. The refractory period is broken into two sections
Refractory Periods
A refractory period is a time at the end of an action potential when another a.p. can NOToccur
The refractory period is broken into two sections
Absolute Refractory Period – impossible to have another a.p.
Relative Refractory Period – possible to have another a.p., but difficult

75. Absolute Refractory Period
Time from the opening of the Na+ activation gates until the closing of inactivation gates
The absolute refractory period:
Prevents the neuron from generating an action potential
Ensures that each action potential is separate
Enforces one-way transmission of nerve impulses
“Absolutely no way to fire another AP”

76. Relative Refractory Period
The interval following the absolute refractory period when:
Sodium gates are closed
Potassium gates are open
Repolarization is occurring
The threshold level is elevated, allowing strong stimuli to increase the frequency of action potential events
“Relatively difficult to have a second AP”

77. Absolute and Relative Refractory Periods
Figure 11.15

78. Conduction Velocities of Axons
Conduction velocities vary widely among neurons
Rate of impulse propagation is determined by:
Axon diameter – the larger the diameter, the faster the impulse
Presence of a myelin sheath – myelination dramatically increases impulse speed
PLAY
InterActive Physiology ®:
Nervous System I: Action Potential, page 17

79. Saltatory Conduction
Current passes through a myelinated axon only at the nodes of Ranvier
Voltage-gated Na+ channels are concentrated at these nodes
Action potentials are triggered only at the nodes and jump from one node to the next
Much faster than conduction along unmyelinated axons

80. Saltatory Conduction
Figure 11.16

81. Multiple Sclerosis (MS)
An autoimmune disease that mainly affects young adults
Symptoms: visual disturbances, weakness, loss of muscular control, and urinary incontinence
Nerve fibers are severed and myelin sheaths in the CNS become nonfunctional scleroses
Shunting and short-circuiting of nerve impulses occurs

82. Multiple Sclerosis: Treatment
The advent of disease-modifying drugs including interferon beta-1a and -1b, Avonex, Betaseran, and Copazone:
Hold symptoms at bay
Reduce complications
Reduce disability