Dr. Michael P. Gillespie

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Membrane Transport and Membrane Potentials

• Dr. Michael P. Gillespie

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Action Potential

• Have the ability to produce action potentials or
  impulses (electrical excitability) in response to
  a stimulus.
• An action potential is an electrical signal that
  propagates from one point to the next along the
  plasma membrane of a neuron.
• A stimulus is any change in the environment that
  is strong enough to initiate an action potential.

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Parts of a Neuron

• Cell Body
• Dendrites
• Axon

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Parts of a Neuron (Cell Body)

• Cell body (perikaryon or soma).
• Contains the nucleus surrounded by cytoplasm
  which contains the organelles.
• Clusters of rough ER called Nissl bodies (produce
  proteins to grow and repair damaged nerves)

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Parts of a Neuron (Nerve Fiber)

• Nerve fiber any neuronal process that emerges
  from the cell body of a neuron.
• Dendrites
• Axon

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Parts of a Neuron (Dendrites)

• Dendrites ( little trees).
• The receiving (input) portion of a neuron.
• Short, tapering, and highly branched.

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Parts of a Neuron (Axon)

• Axon ( axis).
• Each nerve contains a single axon.
• The axon propagates nerve impulses toward another
  neuron, muscle fiber, or gland cell.
• Long, thin, cylindrical projection that often
  joins the cell body at a cone-shaped elevation
  called the axon hillock ( small hill).
• The part of the axon closest to the hillock is
  the initial segment.
• The junction between the axon hillock and the
  initial segment is the trigger zone (nerve
  impulses arise here).
• The cytoplasm of the axon is the axoplasm and is
  surrounded by a plasma membrane known as the
  axolemma (lemma sheath).

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Synapse

• The synapse is the site of communication between
  two neurons or between a neuron and an effector
  cell.
• Synaptic end bulbs and varicosities contain
  synaptic vesicles that store a chemical
  neurotransmitter.

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Myelination

• The myelin sheath is a lipid and protein
  covering. It is produced by the neuroglia.
• The sheath electrically insulates the axon of a
  neuron.
• The sheath increases the speed of nerve impulse
  conduction.
• The amount of myelin increases from birth on.
• Axons without a covering are unmyelinated. Axons
  with a covering are myelinated.

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Myelination Continued

• Two types of neuroglial cells produce
  myelination.
• Schwann cells located in the PNS.
• Oligodendrocytes located in the CNS.

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Neurolemma (Sheath of Schwann)

• The neurolemma (sheath of Schwann) is the outer
  nucleated cytoplasmic layer of the Schwann cell.
• It encloses the myelin sheath.
• It is only found around the axons of the PNS.
• If the axon is injured, the neurolemma forms a
  regeneration tube that guides and stimulates
  re-growth of the axon.

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Nodes of Ranvier

• The nodes of Ranvier are gaps in the myelin
  sheath at intervals along the axon.
• Each Schwann cell wraps one axon segment between
  two nodes.
• The electrical impulse jumps from node to node to
  speed up the propagation
• Nodes of Ranvier are present in the CNS, but
  fewer in number.

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Demyelination

• Demyelination is the loss or destruction of the
  myelin sheaths around axons.
• It occurs as the result of disorders such as
  multiple sclerosis or Tay-Sachs disease.
• Radiation and chemotherapy can also damage the
  myelin sheath.
• Demyelination can deteriorate the affected nerves.

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Electrical Signals in Neurons

• Neurons are electrically excitable and
  communicate with one another using 2 types of
  electrical signals.
• Graded potentials (short distance communication).
• Action potentials ((long distance communication).
• The plasma membrane exhibits a membrane
  potential. The membrane potential is an
  electrical voltage difference across the membrane.

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Electrical Signals in Neurons

• The voltage is termed the resting membrane
  potential.
• The flow of charged particles across the membrane
  is called current.
• In living cells, the flow of ions constitutes the
  electrical current.

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Ion Channels

• The plasma membrane contains many different kinds
  of ion channels.
• The lipid bilayer of the plasma membrane is a
  good electrical insulator.
• The main paths for flow of current across the
  membrane are ion channels.

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Ion Channels

• When ion channels are open, they allow specific
  ions to move across the plasma membrane down
  their electrochemical gradient.
• Ions move from greater areas of concentration to
  lesser areas of concentration.
• Positively charged cations move towards a
  negatively charged area and negatively charged
  anions move towards a positively charged area.
• As they move, they change the membrane potential.

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Ion Channel Gates

• Ion channels open and close due to the presence
  of gates.
• The gate is part of a channel protein that can
  seal the channel pore shut or move aside to open
  the pore.

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Types of Ion Channels

• Leakage channels
• Ligand-gated channel
• Mechanically gated channel
• Voltage gated channel

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Leakage Channels

• Leakage channels gates randomly alternate
  between open and closed positions.
• More potassium ion (K) leakage channels than
  sodium (Na) leakage channels.
• The potassium ion leakage channels are leakier
  than the sodium ion leakage channels.

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Ligand-gated Channel

• Ligand-gated channels open and close in
  response to a specific chemical stimulus.
• Neurotransmitters, hormones, and certain ions can
  act as the chemical stimulus that opens or closes
  these channels.

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Mechanically Gated Channel

• Mechanically gated channels opens or closes in
  response to mechanical stimulation.
• Vibration, touch, pressure, or tissue stretching
  can all distort the channel from its resting
  position, opening the gate.

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Voltage-gated Channel

• Voltage-gated channels opens in response to a
  change in membrane potential (voltage).
• These channels participate in the generation and
  conduction of action potentials.

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Gradients

• Concentration Gradient A difference in the
  concentration of a chemical from one place to
  another.
• Electrochemical Gradient The combination of the
  effects of the concentration gradient and the
  membrane potential.

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Transport Across the Membrane

• Passive Transport does not require cellular
  energy.
• Substances move down their concentration or
  electrochemical gradients using only their own
  kinetic energy.
• Active Transport requires cellular energy in
  the form of ATP.

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3 Types of Passive Transport

• Diffusion through the lipid bilayer.
• Diffusion through membrane channels.
• Facilitated diffusion.

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Diffusion

• Materials diffuse from areas of high
  concentration to areas of low concentration.
• The move down their concentration gradient.
• Equilibrium molecules are mixed uniformly
  throughout the solution.

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Factors Influencing Diffusion

• Steepness of the concentration gradient.
• Temperature.
• Mass of the diffusing substance,
• Surface area.
• Diffusion distance.

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Resting Membrane Potential

• The resting membrane potential occurs due to a
  buildup of negative ions in the cytosol along the
  inside of the membrane and positive ions in the
  extracellular fluid along the outside of the
  membrane.
• The potential energy is measured in millivolts
  (mV).

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Resting Membrane Potential

• In neurons, the resting membrane potential ranges
  from 40 to 90 mV. Typically 70 mV.
• The minus sign indicates that the inside of the
  cell is negative compared to the outside.
• A cell that exhibits a membrane potential is
  polarized.
• The potential exists because of a small buildup
  of negative ions in the cytosol along the inside
  of the membrane and positive ions in the
  extracellular fluid along the membrane.

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Electrochemical Gradient

• An electrical difference and a concentration
  difference across the membrane.

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Factors Producing the Resting Membrane Potential

• Unequal distribution of ions in the ECF and
  cytosol.
• Inability of most anions to leave the cell.
• Electrogenic nature of the Na/K ATPases.

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Unequal distribution of ions in the ECF and
cytosol.

• ECF is rich in Na and CL- ions.
• Cytosol has the cation K and the dominant anions
  are phosphates attached to ATP and amino acids in
  proteins.
• The plasma membrane has more K leakage channels
  than Na leakage channels.

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Inability of most anions to leave the cell.

• The anions are attached to large nondiffusable
  molecules such as ATP and large proteins.

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Electrogenic nature of the Na/K ATPases.

• Membrane permeability to Na is very low because
  there are very few sodium leakage channels.
• Sodium ions do slowly diffuse into the cell,
  which would eventually destroy the resting
  membrane potential.
• Na/K ATPases pump sodium back out of the cell
  and bring potassium back in.
• They pump out 3 Na for every 2 K they bring in.

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Graded Potentials

• A graded potential is a small deviation from the
  resting membrane potential.
• It makes the membrane either more polarized (more
  negative inside) or less polarized (less negative
  inside).
• Most graded potentials occur in the dendrites or
  cell body.

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Graded Potentials

• Hyperpolarizing graded potential make the
  membrane more polarized (inside more negative).
• Depolarizing graded potential make the membrane
  less polarized (inside less negative).
• Graded potentials occur when ligand-gated or
  mechanically gated channels open or close.
• Mechanically gated and ligand-gated channels are
  present in sensory neurons.
• Ligand-gated channels are present in interneurons
  and motor neurons.

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Graded Potentials

• Graded potentials are graded because they vary in
  amplitude (size) depending on the strength of the
  stimulus.
• The amplitude varies depending upon how many
  channels are open and how long they are open.
• The opening and closing of channels produces a
  flow of current that is localized.

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Graded Potentials

• The charge spreads a short distance and dies out
  (decremental conduction).
• The charge can become stronger and last longer by
  adding with other graded potentials (Summation).

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Types of Graded Potentials

• Post-synaptic potentials a graded potential
  that occurs in the dendrites or cell body of a
  neuron in response to a neurotransmitter.
• Receptor potentials and generator potentials
  graded potentials that occur in sensory receptors
  and sensory neurons.

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Action Potentials

• An action potential or impulse is a sequence of
  events that decrease and reverse the membrane
  potential and eventually restore it to its
  resting state.
• Depolarizing phase the resting membrane
  potential becomes less negative, reaches zero,
  and then becomes positive.
• Repolarizing phase restores the resting
  membrane potential to -70 mV.

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Threshold

• Threshold depolarization reaches a certain
  level (about 55 mV), voltage gated channels
  open.
• A weak stimulus that does not bring the membrane
  to threshold is called a sub-threshold stimulus.
• A stimulus that is just strong enough to
  depolarize a membrane is called a threshold
  stimulus.
• Several action potentials will from in response
  to a supra-threshold stimulus.
• Action potentials arise according to an all or
  none principal.

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Depolarizing Phase

• A depolarizing graded potential or some other
  stimulus causes the membrane to reach threshold.
• Voltage-gated ion channels open rapidly.
• The inflow of positive Na ions changes the
  membrane potential from 55mv to 30 mV.
• K channels remain largely closed.
• About 20,000 Na enter through the gates.
  Millions are present in the surrounding fluid.
• Na/K pumps bail them out.

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Repolarizing Phase

• While Na channels are opening during
  depolarization, K channels remain largely
  closed.
• The closing of Na channels and the slow opening
  of K channels allows for repolarization.
• K channels allow outflow of K ions.

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Refractory Period

• The refractory period is the period of time after
  an action potential begins during which an
  excitable cell cannot generate another action
  potential.
• Absolute refractory period a second action
  potential cannot be initiated, even with a very
  strong stimulus.
• Relative refractory period an action potential
  can be initiated, but only with a larger than
  normal stimulus.

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Propagation of Nerve Impulses

• Unlike the graded potential, the impulse in the
  action potential is not detrimental (it does not
  die out).
• The impulse must travel from the trigger zone to
  the axon terminals.
• This process is known as propagation or
  conduction.
• The impulse spreads along the membrane.
• As Na ions flow in, they trigger depolarization
  which opens Na channels in adjacent segments of
  the membrane.

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2 Types of Propagation

• Continuous Conduction step by step
  depolarization and repolarization of each segment
  of the plasma membrane.
• Saltatory Conduction a special mode of action
  potential propagation along myelinated axons.
• The action potential leaps from one Node of
  Ranvier to the next.

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Continuous and Saltatory Conduction

• Few ion channels are present where there is
  myelin.
• Nodes of Ranvier areas where there is no myelin
  contain many ion channels.
• The impulse jumps from node to node.
• This speeds up the propagation of the impulse.
• This is a more energy efficient mode of
  conduction.

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Neurotoxins Local Anesthetics

• Neurotoxins produce poisonous effects upon the
  nervous system.
• Local anesthetics are drugs that block pain and
  other somatic sensations.
• These both act by blocking the opening of
  voltage-gated Na channels and preventing
  propagation of nerve impulses.

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Factors That Affect Speed of Propagation

• 1. Amount of myelination - Myelinated axons
  conduct impulses faster than unmyelinated ones.
• 2. Axon diameter - Larger diameter axons
  propagate impulses faster than smaller ones.
• 3. Temperature Axons propagate action
  potentials at lower speeds when cooled.

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Classification of Nerve Fibers

• A fibers.
• Largest diameter.
• Myelinated.
• Convey touch, pressure, position, thermal
  sensation.

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Classification of Nerve Fibers

• B fibers.
• Smaller diameter than A fibers.
• Myelinated.
• Conduct impulses from the viscera to the brain
  and spinal cord (part of the ANS).

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Classification of Nerve Fibers

• C fibers.
• Smallest diameter.
• Unmyelinated.
• Conduct some sensory impulses and pain impulses
  from the viscera.
• Stimulate the heart, smooth muscle, and glands
  (part of ANS).

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Encoding Intensity of a Stimulus

• A light touch feels different than a firmer touch
  because of the frequency of impulses.
• The number of sensory neurons recruited
  (activated) also determines the intensity of the
  stimulus.

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Signal Transmission at Synapses

• Presynaptic neuron the neuron sending the
  signal.
• Postsynaptic neuron the neuron receiving the
  message.
• Axodendritic from axon to dendrite.
• Axosomatic from axon to soma.
• Axoaxonic from axon to axon.

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Types of Synapses

• Electrical synapse
• Chemical synapse

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Electrical Synapses

• Action potentials conduct directly between
  adjacent cells through gap junctions.

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Electrical Synapses

• Tubular connexons act as tunnels to connect the
  cytosol of the two cells.
• Advantages.
• Faster communication than a chemical synapse.
• Synchronization they can synchronize the
  activity of a group of neurons or muscle fibers.
  In the heart and visceral smooth muscle this
  results in coordinated contraction of these
  muscle fibers.

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Chemical Synapses

• The plasma membranes of a presynaptic and
  postsynaptic neuron in a chemical synapse do not
  touch one another directly.
• The space between the neurons is called a
  synaptic cleft which is filled with interstitial
  fluid.
• A neurotransmitter must diffuse through the
  interstitial fluid in the cleft and bind to
  receptors on the postsynaptic neuron.
• The synaptic delay is about 0.5 msec.

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Removal of Neurotransmitter

• Diffusion.
• Enzymatic degradation.
• Uptake by cells.
• Into the cells that released them (reuptake).
• Into neighboring glial cells (uptake).

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Spatial and Temporal Summation of Postsynaptic
Potentials

• A typical neuron in the CNS receives input from
  1000 to 10,000 synapses.
• Integration of these inputs is known as summation.

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Spatial and Temporal Summation of Postsynaptic
Potentials

• Spatial summation summation results from
  buildup of neurotransmitter released by several
  presynaptic end bulbs.
• Temporal summation summation results from
  buildup of neurotransmitter released by a single
  presynaptic end bulb 2 or more times in rapid
  succession.

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Neural Circuits

• Diverging circuit single presynaptic neuron
  influences several postsynaptic neurons (i.e.
  muscle fibers or gland cells).
• Converging circuit several presynaptic neruons
  influence a single post-synaptic neuron (results
  in a stronger signal).

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Neural Circuits

• Reverberating circuit Branches from later
  neurons stimulate earlier ones (may last for
  seconds to hours) (breathing, coordinated
  muscular activities, waking up, short-term
  memory).
• Parallel after-discharge circuit a presynaptic
  neuron stimulates a group of neurons that all
  interact with a common postsynaptic cell (quick
  stream of impulses) (mathematical calculations).

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Neural Circuits
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Neurogenesis in the CNS

• Birth of new neurons.
• From undifferentiated stem cells.
• Epidermal growth factor stimulates growth of
  neurons and astrocytes.
• Minimal new growth occurs in the CNS.
• Inhibition from glial cells.
• Myelin in the CNS.

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Damage and Repair in the PNS

• Axons and dendrites may undergo repair if the
  cell body is intact, if the Schwann cells are
  functional, and if scar tissue does not form too
  quickly.
• Wallerian degeneration.
• Schwann cells adjacent to the site of injury grow
  torwards one another and form a regeneration tube.

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