AP 150 Introduction to Human Physiology

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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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Electrochemical Gradient of the Neuron Membrane

• 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

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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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Resting Membrane Potential (RMP)

• 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

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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 75xs 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 Ca2
• 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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Action Potentials

• 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
  dont
• 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

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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 11.12.1
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Action Potential Depolarization Phase

• 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

Figure 11.12.2
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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 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 potential Yellow line
permeability of membrane to sodium Green 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 impulse
• on 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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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

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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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Coding for Stimulus Intensity

• 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

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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 summation Fig. B
illustrates temporal summation Fig. 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?