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AP 150 Introduction to Human Physiology

Chapter 12

Neurophysiology

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Parts of the Neuron• Cell Body

– Contains the nucleus

• Dendrites– Receptive regions; transmit impulse to cell

body– Short, often highly branched– May be modified to form receptors

• Axons– Transmit impulses away from cell body– Axon hillock; trigger zone

• Where action potentials first develop– Presynaptic terminals (terminal boutons)

• Contain neurotransmitter substance (NT)

• Release of NT stimulates impulse in next neuron

– Bundles of axons form nerves

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Electrical Signals

• Neurons produce electrical signals called action potentials ( = nerve impulse)

• Nerve impulses transfer information from one part of body to another– e.g., receptor to CNS or CNS to effector

• Electrical properties result from – ionic concentration differences across plasma

membrane – permeability of membrane

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• Electrical Gradient– Develops when there are more positive or negative charges (ions)

on one side of a membrane than on the other

– Charges (ions) move toward the area of opposite charge• Positive toward negative and vice versa

• Chemical Gradient– Develops when there are more ions of a substance in one area than

in another (e.g., more Na+ extracellularly than intracellularly)

– Ions tend to move from an area of high concentration to an area of low concentration; more to less (i.e., down their concentration gradient)

• Electrochemical gradient – The sum of all electrical and chemical forces acting across the cell

membrane

Electrochemical Gradient of the Neuron Membrane

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Electrochemical Gradient of Axon Membrane

• Note sodium ion concentration intracellularly vs. extracellularly• Which is greater? In which direction would Na+ tend to diffuse?

• Note potassium ion concentration intracellularly vs. extracellulary• Which is greater? In which direction would K+ tend to diffuse?

• Note chloride ion concentration intracellularly vs. extracellulary• Which is greater? In which direction would Cl- tend to diffuse?

• Note anionic protein (A-) concentration intracellulary vs. extracellularly• Which is greater? In which direction would A- tend to diffuse?

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An Introduction to the Resting Membrane Potential

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Electrochemical Gradients

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• Nerve cell has an electrical potential, or voltage across its membrane of a –70 mV; (= to 1/20th that of a flashlight battery (1.5 v)

• The potential is generated by different concentrations of Na+, K+, Cl, and protein anions (A)

• But the ionic differences are the consequence of:

– Differential permeability of the axon membrane to these ions

– Operation of a membrane pump called the sodium-potassium pump

Resting Membrane Potential (RMP)

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What Establishes the RMP?

• Diffusion of Na+ and K+ down their concentration gradients– Na+ diffuses into the cell and K+ diffuses out of the cell

• BUT, membrane is 75x’s more permeable to K+ than Na+ – Thus, more K+ diffuses out than Na+ diffuses in

– This increases the number of positive charges on the outside of the membrane relative to the inside.

• BUT, the Na+-K+ pump carries 3 Na+ out for every 2 K+ in.– This is strange in that MORE K+ exited the cell than Na+ entered!

– Pumping more + charges out than in also increases the number of + changes on the outside of the membrane relative to the inside.

• AND presence of anionic proteins (A-) in the cytosol adds to the negativity of the cytosolic side of the membrane

• THEREFORE, the inside of the membrane is measured at a -70 mV (1 mv = one-thousandth of a volt)

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Resting Membrane Potential• Number of charged

molecules and ions inside and outside cell nearly equal

• Concentration of K+ higher inside than outside cell, Na+ higher outside than inside

• Potential difference: unequal distribution of charge exists between the immediate inside and immediate outside of the plasma membrane: -70 to -90 mV

• The resting membrane potential

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Sodium-Potassium Exchange Pump

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Changes in the Membrane Potential

• Membrane potential is dynamic– Rises or falls in response to temporary changes in

membrane permeability– Changes in membrane permeability result from the

opening or closing of membrane channels

• Types of channels– Passive or leak channels - always open– Gated channels - open or close in response to specific

stimuli; 3 major types• Ligand-gated channels• Voltage-gated channels• Mechanically-gated channels

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Nongated (Leakage) channels

• Many more of these for K+ and Cl- than for Na+. – So, at rest, more K+ and Cl- are moving than Na+.

• How are they moving? – Protein repels Cl-, so Cl- moves out.

– K+ are in higher concentration on inside than out, they diffuse out.

– Always open and responsible for permeability when membrane is at rest.

– Specific for one type of ion although not absolute.

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Gated Channels

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Gated Ion Channels

• Gated ion channels. Gated ion channels open and close because of some sort of stimulus. When they open, they change the permeability of the cell membrane.

– Ligand-gated: open or close in response to ligand (a chemical) such as ACh binding to receptor protein.

• Acetylcholine (ACh) binds to acetylcholine receptor on a Na+ channel. Channel opens, Na+ enters the cell.

• Ligand-gated channels most abun- dant on dendrites and cell body; areas where most synaptic commu-nication occurs

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Voltage Gated Ion Channels• Voltage-gated: open or close in response to small

voltage changes across the cell membrane. • At rest, membrane is negative on the inside relative

to the outside. • When cell is stimulated, that relative charge

changes and voltage-gated ion channels either open or close.

• Most common voltage gated are Na+, K+, and Ca+2 • Common on areas where action potentials develop

– Axons of unipolar and multipolar neurons– Sarcolemma (including T-tubules) of skeletal muscle

fibers and cardiac muscle fibers

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Local Potentials/Graded Potentials• Graded: of varying intensity; NOT all the same intensity• Changes in membrane potential that cannot spread far from site

of stimulation• Can result in depolarization or hyperpolarization• Depolarization

– Opening Na+ channels allows more + charges to enter thereby making interior less negative (-70 mV -60mV); see next slide

– RMP shifts toward O mV• Hyperpolarization

– Opening of K+ channels allows more + charges to leave thereby making interior more negative (-70 mV -80 mV); see next slide

– RMP shifts away from O mV• Repolarization

– Process of restoring membrane potential back to normal (RMP)• Degree of depolarization decreases with distance from

stimulation site; called decremental spread (see next slide)• Graded potentials occur on dendrites and cell bodies of neurons

but also on gland cells, sensory receptors, and muscle cell sarcolemma

• Affect only a tiny area (maybe only 1 mm in diameter)– If so, how do neurons trigger release of neurotransmitter far from

dendrites/cell body?

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Changes in Resting Membrane Potential: Ca2+

• Voltage-gated Na+ channels sensitive to changes in extracellular Ca2+ concentrations– If extracellular Ca2+ concentration decreases-

Na+ gates open and membrane depolarizes.– If extracellular concentration of Ca2+ increases-

gates close and membrane repolarizes or becomes hyperpolarized.

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Depolarization and Hyperpolarization

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Depolarization

Hyperpolarization

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Graded Potentials

Graded potentials decrease in strength as they spread out from the point of origin

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• A brief reversal of membrane potential with a total amplitude of 100 mV

• Are triggered only by depolarizations• Depolarization of one part of the membrane triggers depolarization (opening of voltage-gated Na+ channels) of an adjacent part, and so on and so on.

• They do not decrease in strength over distance• Are “all-or-none” events; they occur or they don’t;– Unlike graded potentials, they are NOT weaker or stronger

• They are the principal means of neural communication

• An action potential in the axon of a neuron is a nerve impulse

Action Potentials

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• 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

Action Potential: Resting State

Figure 11.12.1

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• Some stimulus opens Na+ gates and Na+ influx occurs– K+ gates are closed

• Na+ influx causes a reversal of RMP– Interior of membrane now less negative (from -70 mV -55 mV)

• Threshold – a critical level of depolarization (-55 to -50 mV)• At threshold, depolarization becomes self-generating

– I.e., depolarization of one segment leads to depolarization in the next– If threshold is not reached, no action potential develops

Action Potential: Depolarization Phase

Figure 11.12.2

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• 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

Action Potential: Repolarization Phase

Figure 11.12.3

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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 11.12.4

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Phases of the Action Potential• 1 – RESTING STATE

– RMP = -70 mV

• 2 – DEPOLARIZATION– Increased Na+ influx– MP becomes less negative– If threshold is reached,

depolarization continues– Peak reached at +30 mV– Total amplitude = 100 mV

• 3 – REPOLARIZATION– Decreased Na+ influx– Increased K+ efflux– MP becomes more negative

• 4 – HYPERPOLARIZATION– Excess K+ efflux

Blue line = membrane potentialYellow line = permeability of membrane to sodiumGreen line = permeability of membrane to potassium

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The Generation of an Action Potential

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Propagation of an Action Potential along an Unmyelinated Axon

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Action Potential

Propagation

Illustration shows continuous propagation of a nerve impulseon an unmyelinated axon.

• Action potentials occur over the entire surface of the axon membrane.

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Saltatory ConductionImpulse Conduction in Myelinated

Neurons

Most Na+ channels concentrated at nodes. No myelin present.

Leakage of ions from one node to another destabilize the second leading to another action potential in the second node. And so on….

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• 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

Action Potential: Role of the Sodium-Potassium Pump

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Action Potentials • All-or-none principle. No matter how strong the stimulus, as long as it is greater than threshold, then an action potential will occur.

• The amplitude of the de-polarization wave will be the same for all action potentials generated.

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Refractory Period• Sensitivity of area of the membrane to

further stimulation decreases for a time

• Parts– Absolute

• Complete insensitivity exists to another stimulus

• From beginning of action potential until near end of repolarization.

• No matter how large the stimulus, a second action potential cannot be produced.

• Has consequences for function of muscle

– Relative• A stronger-than-threshold stimulus

can initiate another action potential

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Speed of Impulse Conduction• Faster in myelinated than in non-myelinated• In myelinated axons, lipids act as insulation

(the myelin sheath) forcing local currents to jump from node to node

• In myelinated neurons, speed is affected by:– Thickness of myelin sheath– Diameter of axons

• Large-diameter conduct more rapidly than small-diameter. Large diameter axons have greater surface area and more voltage-gated Na+ channels

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Nerve Fiber Types• Type A: large-diameter (4-20 µm), heavily myelinated. Conduct at 15-120 m/s (= 300 mph). – Motor neurons supplying skeletal muscles and most sensory neurons carrying info. about position, balance, delicate touch

• Type B: medium-diameter (2-4 µm), lightly myelinated. Conduct at 3-15 m/s. – Sensory neurons carrying info. about temperature, pain, general touch, pressure sensations

• Type C: small-diameter (0.5-2 µm), unmyelinated. Conduct at 2 m/s or less. – Many sensory neurons and most ANS motor neurons to smooth muscle, cardiac muscle, glands

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• All action potentials are alike (of the same amplitude) and are independent of stimulus intensity.– The amplitude of the action potential is the same for a

weak stimulus as it is for a strong stimulus.

• So how does one stimulus feel stronger than another?– Strong stimuli generate more action potentials than

weaker stimuli.– More action potentials stimulate the release of more

neurotransmitter from the synaptic knob

• The CNS determines stimulus intensity by the frequency of impulse transmission

Coding for Stimulus Intensity

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Frequency of Action Potentials

Figure 8-13: Coding for stimulus intensity

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Trigger Zone: Cell Integration and Initiation of AP

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Trigger Zone: Cell Integration and Initiation of AP

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Trigger Zone: Cell Integration and Initiation of AP

• Excitatory signal: – Opening of Na+ channels– Depolarizes membrane (-70 mV -60 mV)– Brings membrane closer to threshold– More likely to give rise to an action potential

• Inhibitory signal– Opening of K+ channels– Hyperpolarizes the membrane (-70 mV -80 mV)

– Takes membrane further from threshold– Less likely to give rise to an action potential

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Postsynaptic Potentials

• Excitatory postsynaptic potential (EPSP)– Depolarization occurs and

response stimulatory– Depolarization might reach

threshold producing an action potential and cell response

• Inhibitory postsynaptic potential (IPSP)– Hyperpolarization and

response inhibitory– Decrease action potentials by

moving membrane potential farther from threshold

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SUMMATION• Individual EPSP has a small

effect on membrane potential– Produce a depolarization of about 0.5

mV

– Could never result in an AP

• Individual EPSPs can combine through summation– Integrates the effects of all the graded

potentials

– GPs may be EPSPs, IPSPs, or both

– Two types of summation• Temporal summation

• Spatial summation

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Summation

Fig. A illustrates spatial summationFig. B illustrates temporal summationFig. C shows both EPSPs and IPSPs affecting the membrane

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Neuronal Pathways and Circuits

• Organization of neurons in CNS varies in complexity– Convergent pathways: several neurons converge on a single postsynaptic neuron. E.g., synthesis of data in brain.

– Divergent pathways: the spread of information from one neuron to several neurons. E.g., important information can be transmitted to many parts of the brain.

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Oscillating Circuits

• Oscillating circuits: Arranged in circular fashion to allow action potentials to cause a neuron in a farther along circuit to produce an action potential more than once. Can be a single neuron or a group of neurons that are self stimulating. Continue until neurons are fatigued or until inhibited by other neurons. Respiration? Wake/sleep?