Neurophysiology Part One

1
Neurophysiology Part One

• Anatomy Organization
• Membrane Excitation
• Electrical Electro Chemical Properties
• Action Resting Potentials

2
Neuronal Structure, Function Organization

• Neuron are highly specialized cells to receive,
  process and transmit information with high
  fidelity without loss of signal strength over
  distance
• Basic structure soma (cell body) thin fibers
  emanating from soma (nerve processes) 2 types
• Multiple dendrites a single axon
• Dendrites (many branches the more branches, the
  more input from many other neurons) receive
  information axon conducts signal from soma
  (tend to be longer) ending in axon terminals to
  other neurons, glands or muscles myelin sheath

3
Signal TransmissionMotor-neuron as an Example

• plasma membrane of dendrites soma receive
  signal from (innervation) terminals of other
  neurons
• Spike-initiating zone (specific region of
  membrane) integrates signal thus determines if
  neuron will generate its own signal (action
  potential or AP)
• In AP the voltage across membrane rapidly rises
  falls spike/nerve impulse
• Axon carries AP from point of origin to axon
  terminals to skeletal muscle fibers
• Some spike-initiating zones axon hillocks near
  soma

4
Physiological Behavior

• Depends on passive electrical properties e.g.
  capacitance resistance (like other electrical
  conductors discussed later) active electrical
  properties allow conduction without decrement
  (no loss of signal strength)
• Active properties depend on presence of
  voltage-gated ion channels in plasma membrane
  (specific proteins) allowing ions to move across
  membrane in regulated fashion ion channels
  localized to special regions having specialized
  signaling functions e.g. axon membrane is
  specialized for conduction of APs by having
  fast-acting, voltage-gated ion channels
  selectively allowing Na K to cross membrane

5
Transmission between Neurons

• Sensory neurons collect info externally/internally
  send it to other neurons sensory axons called
  afferent fibers (carry signal inward toward
  higher processing centers)
• Interneurons most numerous type lie entirely
  within CNS carry info between other neurons
  info exchanged at special locations (synapses)
• To respond to info, neurons at effector organs
  (e.g. muscle, gland) must be activated
  neurons/fibers carrying info from effector organs
  efferents
• Afferents interneurons efferents the
  synapses in between neural circuit

6
Some terminology

• Presynaptic and post-synaptic neurons
• Neurotransmitters specific molecules released
  from pre-synaptic axon terminals in response to
  the APs in its axon ( carries transmission to
  the next neuron)
• Plasma membrane of post-synaptic neuronal soma
  dendrites contain ligand-gated ion channels
  bind neurotransmitters cause postsynaptic cell
  to respond to presence of the chemical signal
• s signals must be integrated to produce change
  in membrane potential at spike-initiating zone
• All-or-none signals (amplitude of signal
  invariant) vs. gradient signals (amplitude of
  signal varies with stimulus strength or other
  variable)

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Organization

• Neurons glia cells
• Neurons sensory, interneurons and motor
• Sensory transform energy of stimulus into
  electrical signals
• Interneurons exchange info perform complex
  computations producing thought behavior
• Motor output, carrying specific instructions to
  muscles or glands
• Gathered in clusters somata of most in CNS
  brain nerve cord (invertebrates brain
  ganglia vertebrates have ganglia outside CNS
  spinal cord)

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Organization cont

• Glia cells (neuroglia) fill space between
  neurons (except for thin fluid-filled space)
• More complex animals more neuroglia
• 10x-50x more neuroglia than neurons vertebrates
  occupy volume of CNS
• Generally dont produce APs

9
Glia Cells Function ?

• Possibilities
• structural metabolic support for neurons some
  glia oligodentrocytes (CNS) Schwann cells
  (periphery) wrap axons in an insulting myelin
  sheath contributes to reliable rapid
  transmission of APs and/or
• help regulate concentration of K pH of
  fluid-filled spaces - highly perm to K
  build-up of K deleterious for neuron and/or
• remove neurotransmitters from extracellular space
  limits time of neurotransmitters action)

10
Membrane Excitation

• Stable voltage (electric potential difference)
  exists across plasma membrane of all animal cells
  however, only membranes of electrically excitable
  cells (neurons/muscle fibers) can respond to
  changes in transmembrane potential differences by
  generating APs
• Membrane potential (difference across the
  membrane) measured in volts

11
More Terminology

• Hyperpolarization increase in potential
  difference across plasma membrane when current
  pulse causes positive charge to exit i.e.
  interior of cell becomes more negative - cell
  membrane responds passively
• Depolarization decrease in potential difference
  across plasma membrane if current pulse causes
  addition of positive charge to interior of cell
  some voltage-gated channels selectively perm to
  Na to open if sufficiently depolarized, AP is
  triggered) - Threshold potential the value of
  the membrane potential where an AP is triggered
  50 of time

12
Role/Types of Ion Channels

• ion selectivity (electrochemical gradient
  specific to certain ions e.g. Na, K)
• voltage-gated (produce APs open when plasma
  membrane depolarizes)
• leak (maintain resting potential where passive
  change occurs during hyperpolarization mostly
  K)
• ligand-gated (bind to messenger molecules e.g.
  neurotransmitters)

13
Passive Electrical Properties

• Lipid bilayer impermeable to ions acts as
  insulator forming an electrical capacitor (stores
  energy in form of separated electric charges)
  channel proteins allow ions to pass across
  membrane give it its electrical conductance
• Resistance (R) Conductance (g) R of membrane
  measure of impermeability to ions g
  permeability R 1/g i.e. the lower the
  resistance, the greater the conductance more
  ionic charges cross open ion channels/time
  Ohms law pertains voltage drop produced across
  membrane by a current that passes through it is
  directly proportional current x resistance of the
  membrane (Vm I x R) total R encountered by
  current flowing into out of cell input R

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Passive Electrical Properties cont

• Capacitance ability of membrane to store
  electrical charge movement of ions up to one
  side of membrane away from the other ionic
  current interactions between oppositely charged
  ions accumulating on both sides of membrane is
  strong because membrane is thin
• Dielectric constant property reflects inherent
  ability of a particular capacitor to store charge

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Electrochemical Potentials

• Defn voltage difference across plasma membrane
  that depends on
• Concentration of various ions is different on
  either side of membrane concentration gradient
  maintained at the expense of metabolic energy
• Ion channels are selectively perm to ions
• 1 2 result in membrane potential membrane
  potential passive electrical properties basis
  of signaling by neurons

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Electrochemical Potentials cont

• Equilibrium potential voltage difference across
  a semi-permeable at which an ion can diffuse
  across is in electrochemical equilibrium (depends
  on concentration gradient) if energy is
  required to maintain a potential, it is not an
  equilibrium state but a steady state (e.g.
  dynamic equilibrium) membrane resting potential
  is a steady-state potential
• Various laws of physics/electrical formulas
  apply to membranes, cells conduction of signals

17
Resting Potential

• Every cell in its non-excited or resting state
  has a potential difference (Vrest) across
  membrane governed by 2 factors
• Presence of open selective ion channels Resting
  Potentials of muscle, nerve and other cells found
  to be far more sensitive to changes in K than
  other ion consistent with high perm of plasma
  membranes to K and this depends on K selective
  leak channels which remain open in the resting
  membrane
• Unequal distribution of inorganic ions between
  cells interior exterior (maintained by active
  transport esp. Na/K pump see Fig 5-15 p. 132
  Donnan equilibrium)

18
Action Potential

• Most neurons use the AP to send info along the
  axon and APs in nervous system basis of
  sensation, memory?, thought ...
• AP large, brief change in Vm propagated along
  axon ( over great distances) without decrement
  production of AP depends on 3 key elements

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Action Potential cont

• Active transport of ions by specific proteins in
  plasma membrane generates asymmetric
  concentrations of ions across membrane
• Unequal distribution of ions generates
  electrochemical gradient across membrane
  providing a reservoir of potential energy
• Electrochemical gradient drives ions across
  membrane when ion-selective channels open, making
  mem. Perm. to certain ions this ionic current
  dramatically changes Vm

20
General Properties of APs

• Threshold current intensity of stimulating
  current sufficient to bring membrane to its
  threshold potential elicit an AP not usually
  measurable in an absolute amount
• once threshold potential reached, AP becomes
  regenerative event becomes self-perpetuating
  Vm continues to become more inside-positive
  without further stimulation reaching a peak
  (brief time called overshoot - neurons
  millisecond cardiac ½ second) after peak, Vm
  drops to ( goes beyond) its more negative state
  also transient called hyperpolarization or
  undershoot)

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General Properties of APs cont

• Refractory brief time after AP when another AP
  cannot be initiated (absolute refractory period)
  if stim. delivered slightly later, AP may be
  initiated but the amplitude may be smaller than
  usual generally the threshold potential is
  higher during this time relative refractory
  period (all-or-nothing doesnt apply here) toilet
  flush analogy
• Accommodation temporary increase in threshold
  that develops during the course of a stimulus

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Accommodation cont

• Determines how individual neurons respond to
  input whether they are continuously active or
  produce only bursts of APs
• Phasic response when stimulated continuously by
  a current of constant intensity, some neurons
  accommodate rapidly generate only 1 or 2 APs at
  beginning of stim.
• Tonic response when accommodating more slowly
  fire repeatedly although with gradually
  decreasing frequency in response to a prolonged
  constant stim

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Accommodation cont

• reduction in frequency of APs typically seen in
  neurons responding tonically during a sustained
  stimulus, visible as increasing distance between
  APs, is adaptation

24
Review

• at rest the membrane most perm to K, but in
  early phase of AP, it becomes more perm to Na
  than to K at rest
• inc. perm strong force pushing Na into cell
  spurt of charge enters cell less
  inside-negative
• when voltage-gated Na channels close perm to
  Na drops, mem. more perm to K than is at rest,
  because voltage-gated K channels are still open
• later, perm to K drops back to resting value
  with only passive leak channels remaining open

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A Closer Look at Ion Channels

• 4 key features of ion channels
• Distribution of ion channels in neuronal
  membranes
• Nature of current flow through a single channel
• Mechanism by which depolarization of membrane
  opens a voltage-gated channel
• Physical basis for channel selectivity
• (Molecular structure has been determined only
  recently seems homologous in structure across
  many species and yet it heterogeneity shows many
  genes are expressed)

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Voltage-gated Na Channels

• Na channels occupy only small fraction of total
  surface area however, each channel can pass a
  very large amount of Na per second provides
  sufficient Na to account for macroscopic
  currents
• 1 activated Na channel carries Na ions at a
  rate of 10,000 ions per millisecond driving
  force as an AP gets underway summed activity
  (I.e. opening closings) of 1000s of Na
  channels, each allowing a minute unitary current
  (i.e. current through a single channel) to cross
  membrane gives rise to macroscopic current

27
Voltage-gated Na Channels cont

• Gating occurs in distinct steps (Fig 5-22 p. 142)
• Activation inactivation of the channel are
  coupled processes
• Selectivity filter area of channel that
  determines its selectivity (based on size,
  charge, level of hydration, etc.)

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Voltage-gated Na Channels overview of activity

• During AP, Na channels respond to an initial
  depolarization by opening allows Na to enter
  cell this further depolarizes the membrane
  which cause more channels to open allowing more
  Na to enter creates an explosive, regenerative
  event once AP starts, needs no more stimulus
• Relationship between membrane potential Na
  conductance (Hodgkin cycle) is e.g. of feedback
• As membrane potential reaches equilibrium
  potential, driving force on Na is reduced, so
  less Na is driven into the cell open Na
  channels become inactivated after time

29
Voltage-gated K Channels

• Respond more slowly to voltage changes
• Membrane conductance increases very little until
  AP near its peak remains elevated during
  falling phase
• Properties vary more than Na channels
• Rapid membrane repolarization produced by current
  through K channels does shorten the AP, allowing
  neurons to generate APs at a higher frequency
  than they otherwise could
• Falling phase of AP depends on inactivation of
  Na channels continued activation of K channels