Transcript P215 - Basic Human Physiology

Computer Simulation of
Neurophysiology
Presented in Lab
Computer Simulation of
Neurophysiology
• Action Potential Stimulation
– Determine threshold
– Observe effects of other stimuli
• Effects of Drugs
• Determination of Conduction Velocity
Action Potential Generation:
Stimulus
• Action potentials are triggered by membrane
depolarization at the axon hillock
• Depolarization caused by increased permeability
to ions
• Permeability typically increased by chemically-or
physically-gated ion channels
• Can also be affected by membrane perturbations,
changes in ion gradients, etc.
Threshold and “All or None”
• Action potentials are driven by
the opening of voltage-gated
ion channels
• Require a minimum amount of
depolarization for any to open
= threshold
• Once some open, they in turn
cause others to open
• “All or none” response for
single neurons
Threshold
Stimulus Intensity
Neuron Axon Response
Compound Action Potentials
• Extracellular recordings of
whole nerve segments
– Many axons w/ variable
thresholds
– Different degrees of
stimulation
• Amplitude of Action
Potential varies with
stimulus strength
• Vary NUMBER of axons
undergoing AP
• Does NOT violate “all or
none” principle
Stimulus Intensity
Action Potential Amplitude
Compound Action Potentials
• Subthreshold stimulus
– No AP
subtheshold
threshold
maximal
submaximal
• Threshold stimulus
– Minimal compound AP
• Submaximal stimulus
Stimulus Intensity
– Variable number of axons
undergo AP
– Variable amplitude
• Maximal stimulus
– Maximum amplitude
– Does not vary with stim
strength
Action Potential Amplitude
Nerve signaling and drugs
• Signal conduction within a
neuron occurs through
action potentials
– voltage-gated channels
• Signal conduction from one
nerve to another occurs
through synapses
– Chemically gated channels
• Neurotoxins could affect
nerve signaling at either site
Neurotoxins
• Affect voltage-gated ion channels (alter APs)
– Tetradotoxin, novocain – block v.g. Na+channels
– Scorpion venoms – keep Na+ channels open and
K+ channels closed (prolonged depolarization)
– Chlorform – open K+channels
(hyperpolarization)
Neurotoxins
• Affect chemistry at synapses (alter normal
AP-inducing stimuli)
– Botulinum toxin (Botox) – prevents vesicle
release from somatic motor neurons
– Latrotoxin (Black widows) – triggers excessive
vesicle release from somatic motor neurons
– Cobratoxin (Cobras) – blocks nicotinic
receptors
Factors Affecting Signal
Conduction: Myelination
• myelin = lipid insulator
– PM of Schwann cells or
oligodendrocytes
• Signals “jump” from one
node to the next (saltatory
conduction)
– AP conduction speed
http://www.blackwellscience.com/matthews/actionp.html
Factors Affecting Signal
Conduction: Axon Diameter
• Cable Theory
– resistance to current increases with decreased
diameter
– resistance slows current
• Therefore:
– Conduction Velocity a 1/Resistance
– Diameter a 1/Resistance
– Conduction velocity a Diameter
Neurophysiology
Background Material
(Not Presented in Lab)
Resting Potential
• Inside of cell negative relative
to the outside (-70 mV)
• [Na+] higher outside than
inside
• [K+] higher inside than
outside
• At RP, neither K+ nor Na+ are
in equilibrium
Action Potentials
• begins at the axon hillock,
travels down axon
• brief, rapid reversal of MP
– Opening of voltage-gated
Na+ and K+ channels
• Self propagating
• All or none
Action Potential Function
(Depolarization)
• Triggering event causes
membrane to depolarize
• slow increase until threshold is
reached
• voltage-gated Na+ channels open
–
–
–
–
Na+ enters cell
further depolarization
more channels open
further depolarization
• membrane reverses polarity
(+30 mV)
Action Potential Function
(Repolarization)
• V.G. Na+ channels close
• Delayed opening of V.G.
K+ channels
– reach peak permeability as
Na+ channels close
• K+ rushes out of the cell
– membrane potential restored
• K+ channels close
• [Na+] and [K+] restored by
the Na+-K+ pump
Cartoons!
http://www.blackwellscience.com/m
atthews/channel.html
Action Potentials
• AP duration ~ 1-2 ms
• response of the nerve cell to the
stimulus is “all or none”
– Amt of depolarization always
the same
– differences in stimulus
intensity are detected by
• The number of neurons
undergoing AP in response to
the stimulus
• The frequency of action
potential generation
Action Potential Propagation
• Na+ moving into one
segment of the neuron
quickly moves laterally
inside the cell
• Depolarizes adjacent
segment to threshold
http://www.blackwellscience.com/matthews/actionp.html
Chemical Synapses
• presynaptic neuron
– synaptic terminal bouton
– contains synaptic vesicles
filled with neurotransmitter
• synaptic cleft
– space in-between cells
• postsynaptic neuron
– Subsynaptic membrane
– Receptor proteins for
neurotransmitter
Chemical Synapses
• AP in terminal opens Ca2+
channels
– Ca2+ rushes in.
• Ca2+ causes vesicles to fuse
to PM and release contents
• Transmitter diffuses across
synaptic cleft and binds to
receptors on subsynaptic
membrane
Chemical Synapses
• Specific ion channels in
subsynaptic membrane open
– chemically-gated ion channels
• Ions enter postsynaptic cell
– graded potential forms
• If graded potential is strong
enough to reach threshold,
generates action potential in
postsynaptic cell
Cartoon!
http://www.blackwellscience.com/ma
tthews/nmj.html
Types of Chemical Synapse
• Excitatory chemical
synapse:
– excitatory postsynaptic
potentials (EPSPs)
– Small depolarization of
postsynaptic neuron
• closer to threshold
http://www.blackwellscience.com/matthews/neurotrans.html
Types of Chemical Synapse
• Inhibitory chemical
synapse:
– inhibitory postsynaptic
potentials (IPSPs)
– Small hyperpolarization
of postsynaptic neuron
• further from threshold
http://www.blackwellscience.com/matthews/neurotrans.htm
l
Synaptic Integration
• Multiple synaptic events have an additive
effect on membrane potential
– summation
• Sum of inputs determines whether axon
hillock depolarized enough for AP to form.
Spatial Summation
• numerous presynaptic fibers
may converge on a single
postsynaptic neuron
• additive effects of
numerous neurons inducing
EPSPs and IPSPs on the
postsyn. neuron
Temporal Summation
threshold
• additive effects of EPSPs and
IPSPs occurring in rapid
succession
• next synaptic event occurs
before membrane recovers
from previous event
membrane
potential
stimulus
Low Frequency Stimulation
threshold
membrane
potential
stimulus
High Frequency Stimulation