PHYSIOLOGY

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PHYSIOLOGY

• Nervous System

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Types of Neurons

• Afferent
• Sensory
• Efferent
• Motor
• Interneurons also known as association neurons
• Between neuron

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Classes of Sensory Receptors also known as
Neurons     Mechano-receptors  mechanical
forces- stretching alters membrane
permeability                 (1)   hair cells 
(deflection depolarization AP's)             
           ie. lateral line of fish
(mechanoreceptor neuromasts detect water
movement, etc)             (2)   stretch
receptors of muscles            (3)  
equilibrium receptor of inner ear           
(4)   receptors of skin (touch, pain, cold,
heat).           Chemo-receptors  chemicals
sense solutes in solvents, taste, smell    
Osmo-receptors  of hypothalamus which monitors
blood osmotic pressure     Photo-receptors
 light - eye, eyespots, infrared receptors of
snakes, etc.     Thermo-receptors  radiant
(heat) energy     Phono-receptors  sound
waves     Electro-receptors  detect electric
currents... electric eels, etc..    
Nociceptors  pain receptors... naked dendrites
of skin (epidermis)              
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Neuroglial Cells of the CNS
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Astrocytes

• In the CNS only
• Most abundant Neuroglial Cell
• Formation of Synapses
• Plays a role in making exchanges between
  capillaries and neurons
• Helps to form the Blood Brain Barrier
• The BBB protects the brain from intruders

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Astrocytes
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Microglial Cells

• Macrophage
• Scavenges apoptotic cells
• May go bad causing Alzheimers Disease
• Excessive secretion of Interleukin-1
• Helps to maintain homeostasis in the brain

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Ependymal Cells of the CNS
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Ependymal Cells

• Lines ventricles in the brain and the central
  cavity of the spinal cord
• Cells have cilia
• Used to circulate the cerebrospinal fluid

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Oligodendrocyte Cells of the CNS
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Oligodendrocyte

• Oligodendrocytes
• Production of myelin in the CNS
• Can cover as many as 60 neurons with myelin

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Schwann/Satellite Cells

• Schwann Cells
• Production of myelin in the PNS
• Not able to cover one neuron, must use multiple
  Schwann Cells
• Formation of the Nodes of Ranvier
• Produces Neuronal Growth Factor
• Satellite Cells
• Function unknown

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Myelin Sheath

• Myelin
• Insulates the axon for rapid conduction of action
  potentials
• Nodes of Ranvier
• Gray v. White matter in the brain
• Multiple Sclerosis is an autoimmune disease

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• http//www.youtube.com/watch?vNaecv3h868c

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Neuron

• Receptive Zone
• Where the Graded Response occurs
• Cell Body
• Same information as a regular cell but no
  centrioles
• Amitotic
• Contains ligand regulated gates
• Dendrites
• Projections to help form synapses
• Contains ligand regulated gates

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Neuron

• Conducting Zone
• Axon Hillock
• Begins action potentials
• Accumulation of K ions
• Contains voltage regulated gates for Na/K
• Axon
• Propagation of action potentials
• Contains voltage regulated gates for Na/K
• Anterograde vs. Retrograde and Polio

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Secretory Zone

• Terminal Boutons
• Contains voltage regulated gates for Ca2
• Contains vesicles filled with Neurotransmitter

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Resting Membrane Potential

• -70 mV
• Membrane is said to be polarized
• Voltage generated by ionic movement through the
  membrane
• Creates a current
• Current Voltage/ Resistance
• Current generates a Kinetic Energy
• More Na on the outside of the cell
• More K on the inside of the cell
• Diffusion down their electrochemical gradient

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Resting Membrane Potential

• Maintained by the Na/KATPase pumps
• Will not allow the neuron to reach equilibrium
  across the membrane
• Actively transports 3Na out of the cell and 2K
  into the cell

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Graded Response

• Short lived
• Localized changes in membrane potential
• Can depolarize or hyperpolarize the membrane
• Dependent on IPSP or EPSP
• The magnitude of the graded potential varies
  directly with the stimulus strength
• The stronger stimulus causes greater voltage
  change and the current flows farther
• The current dies out within a few millimeters of
  its origin
• Graded response only signals over a very short
  distance

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Graded Response

• Ligand sensitive Na gates will open with a
  stimulus
• Na diffuses into the cell down its
  electrochemical gradient
• Depolarization of the membrane
• K is repelled down the membrane towards the axon
  hillock
• K can diffuse out of the cell because the plasma
  membrane is very leaky

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Action Potentials

• Begins at the axon hillock
• Voltage regulated Na and K gates
• Along with Na/KATPase pumps along the entire
  membrane
• All or nothing response

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Action Potentials

• Depolarization
• -50mV due to the accumulation of K at the axon
  hillock triggers an action potential
• At -50mV Na voltage regulated gates open
• Na diffuses into the cell down its
  electrochemical gradient
• Na repels K down the membrane
• Positive Feedback on
• The more positive the voltage, due to Na
  diffusing into the cell, the more Na gates open.
  This creates a more positive voltage and more
  Na gates open
• Positive Feedback off
• 30mV

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Action Potential

• Repolarization
• At 30mV
• All Na gates close quickly
• All K gates open
• K diffuses out of the cell down its
  electrochemical gradient
• K gates close slowly at -70mV
• K continues to diffuse out of the cell until it
  reaches -90mV
• All K gates are closed

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Action Potential

• Hyperpolarization
• At -90mV the Na/KATPase pump turns on
• Pumps 3Na out and 2K into the cell
• Re-establishes resting membrane potential

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Propagation of an Action Potential

• As the influx of Na repels the K down the
  membrane there is an accumulation of K
• The K accumulation with change the membrane
  voltage to -50mV
• The occurs when the previous action potential
  reaches 30mV
• Repolarization is chasing Depolarization down the
  membrane

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Refractory Period

• Absolute refractory
• From the opening of the Na channels until the
  Na channels begin to reset to their original
  resting state
• Cannot re-stimulate the neuron during this time
• Relative refractory
• The interval following the absolute refractory
  period
• Na channels have returned to their resting state
• K channels are still open and repolarizing the
  membrane
• Can re-stimulate the neuron during this time with
  a great stimulus

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Synapse

• Presynaptic neuron
• Postsynaptic neuron
• Synaptic Cleft
• About 10 angstroms between neurons
• Synaptic Vesicles
• Filled with neurotransmitter

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Synapse

• Voltage regulated Calcium channels
• Membrane reaches -50mV due the accumulation of K
• Calcium channels open
• Calcium diffuses in down its electrochemical
  gradient
• 2 Calcium ions bind to the vesicle
• The vesicle fuses with the membrane for
  exocytosis of the NT

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Synapse

• The Neurotransmitter crosses the synaptic cleft
• NT binds to the receptors on the postsynaptic
  neuron
• Neurotransmitter are removed from the synaptic
  cleft by
• Reuptake
• Phagocytosis
• Enzymatic Degradation

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Events at the Synapse
AP reaches axon terminal Voltage-gated Ca2
channels open Ca2 entry Exocytosis of
neurotransmitter containing vesicles
Ca2 Signal for Neurotransmitter Release
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1. Axon Diameter
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Fig. 8-18
2. Signal Transduction in Myelinated Axon
Animation
Demyelination diseases (E.g. ?)
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3 Classes of Neurotransmitters (of 7)

• Acetyl Choline (ACh)
• Made from Acetyl CoA and choline
• Synthesized in axon terminal
• Quickly degraded by ACh-esterase
• Cholinergic neurons and receptors Nicotinic
  (agonistic) and muscarinic (antagonist)
• Amines
• Serotonin (tryptophane) and Histamine (histidine)
• SSRI antidepressants
• Dopamine and Norepinephrine (tyrosine)
• Widely used in brain, role in emotional behavior
  (NE used in ANS)
• Adrenergic neurons and receptors - ? and ?
• Gases
• NO (nitric oxide) and CO
• Others AA, (e.g., GABA), lipids, peptides,
  purines

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Neurotransmitters

• Cholinergic Receptors
• Nicotinic
• Muscarinic
• Catecholamine
• Alpha
• Beta

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Nicotinic Receptors

• Stimulated by ACh and nicotine, not stimulated by
  muscarine.
• Found at all ganglionic synapses.
• Also found at neuromuscular junctions.
• A ligand sensitive gate

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Muscarinic Receptors

• Stimulated by ACh and muscarine, not stimulated
  by nicotine.
• Found at target organs when ACh is released by
  post-ganglionic neurons (all of parasympathetic,
  and some sympathetic).
• Stimulated selectively by Muscarine, Bethanechol.
  
• Blocked by Atropine.
• Stimulation causes
• Increased sweating.
• Decreased heart rate.
• Decreased blood pressure due to decreased cardiac
  output.
• Bronchoconstriction and increased
  bronchosecretion.
• Contraction of the pupils, and contraction of
  ciliary body for near vision.
• Tearing and salivation.
• Increased motility and secretions of the GI
  system.
• Urination and defecation.
• Engorgement of genitalia.

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Catecholamine Receptors

• NE and epinephrine, each act on a- and
  ß-adrenergic receptors
• Two subclasses of a-adrenergic receptors
• Activation of a1-receptors usually results in a
  slow depolarization linked to the inhibition of
  K channels
• activation of a2-receptors produces a slow
  hyperpolarization due to the activation of a
  different type of K channel.
• There are three subtypes of ß-adrenergic receptor
• Agonists and antagonists of adrenergic receptors
• ß-blocker propanolol (Inderol).
• However, most of their actions are on smooth
  muscle receptors, particularly the cardiovascular
  and respiratory systems

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a1 adrenergic receptors
edit Comparison

• Mainly involved with contraction of smooth muscle
• G protein, cAMP action

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a2 adrenergic receptors

• Three types of receptors
• a2A, a2?, and a2C
• These receptors have a critical role in
  regulating neurotransmitter release from
  sympathetic nerves and from adrenergic neurons in
  the central nervous system

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ß1 adrenergic receptors

• Specific actions of the ß1 receptor include
• Increases cardiac output
• by raising heart rate and increasing the volume
  expelled with each beat (increased ejection
  fraction).
• Renin release from juxtaglomerular cells.
• Lipolysis in adipose tissue.

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ß2 adrenergic receptors

• Specific actions of the ß2 receptor include
• Smooth muscle relaxation, e.g. in bronchi.
• Relax non-pregnant uterus.
• Relax detrusor urinae muscle? of bladder wall
• Dilate arteries to skeletal muscle
• Glycogenolysis and gluconeogenesis
• Contract sphincters of GI tract
• Thickened secretions from salivary glands.
• Inhibit histamine-release from mast cells
• Increase renin secretion from kidney

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ß3 adrenergic receptors

• Specific actions of the ß3 receptor include
• Enhancement of lipolysis in adipose tissue.
• CNS effects

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Neurological Communication

• Theres no one-to-one communication between
  neurons
• May be as many as 500 neurons communicating with
  a single neuron
• Convergence
• Divergence

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Postsynaptic Responses
Can lead to either EPSP or IPSP Any one synapse
can only be either excitatory or inhibitory Fast
synaptic potentials Opening of chemically gated
ion channel Rapid of short duration Slow
synaptic potentials Involve G-proteins and 2nd
messengers Can open or close channels or change
protein composition of neuron
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Integration of Neural InformationTransfer
Multiple graded potentials are integrated at axon
hillock to evaluate necessity of AP 1. Spatial
Summation stimuli from different locations are
added up 2. Temporal Summation sequential
stimuli added up
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1. Spatial Summation
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2. Temporal Summation
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General Adaptation Syndrome
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General Adaptation Syndrome

• Hans Selye
• Alarm Phase
• A stressor disturbs homeostasis
• Cerebral Cortex alerts Hypothalamus which alerts
  the Sympathetic Nervous System

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General Adaptation Syndrome

• Resistance Phase
• Body reacts to stressor
• Attempts to return to homeostasis
• Down and Up Regulation

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General Adaptation Syndrome

• Exhaustion Phase
• Physical and Psychological energy is sapped
• Atypical depression
• Mood disorder
• Dysphoria -generally characterized as an
  unpleasant or uncomfortable mood, such as sadness
  (depressed mood), anxiety, irritability, or
  restlessness
• Serious illness(es) may occur
• Hits person at weakest genetic point
• Autoimmune Disease(s)
• Endorphins Increase and inhibit the immune system
  response

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General Adaptation Syndrome

• Final Phase is Death

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Dermatomes
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Dermatomes
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Bipolar Neuron

• Two processes
• An axon and a dendrite
• They extend in opposite directions
• Used for sensory organs
• Olfactory neurons
• Retina

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Unipolar Neurons

• Presence of only a single axon, branching at the
  terminal end.
• True unipolar neurons not found in adult human
  common in human embryos and invertebrates