Transcript Cell Membranes II

Physiology of a Neuron
From Dendrite to synaptic
transmission
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Outline
I.
Dendrites
A. Graded potentials
i. EPSP
ii. IPSP
B. Summation- temporal and spatial
II.
Axon
A. Action potentials
B. Refractory periods
C. Myelination
III.
Synapse
A. Voltage gated calcium channels
B. Neurotransmitters
IV. Functional classification of receptors
A. Ionotropic
B. Metabotropic
i. Second messengers
V. Drugs that induce spastic or flaccid paralysis
Neuron anatomy
• Draw and label a neuron
– Dendrite - projections from
the soma
• the sensory portion of the neuron
– Soma - main body of the
neuron
– Axon hillock- trigger zone
– Axon - extends from soma to
the terminal
• the effector part of the neuron
– Terminal bouton/ axonal
terminus/synaptic terminal
– Synaptic vesicles
– Synaptic cleft
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Function of Dendrites in Stimulating Neurons
• Dendrites spaced in all directions from
neuronal soma.
– allows signal reception from a large
spatial area providing the opportunity
for summation of signals from many
presynaptic neurons
• Dendrites transmit signals by graded
local potentials from opening of LGC’s
• LGC (Ligand-gated channels): are not
dependent on membrane potential but
binding of ligands (e.g.
neurotransmitters)
– Neurotransmitter receptors
– Located on dendrites and cell body
– Intensity of potential diffuses away
from stimulus
Axon
hillock
LGC’s
VGC’s
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Types of Ligand Gated Channels (LGC’s)
Pore loop- amino acids here control ion selectivity, what
passes
Gene Families- many different channel genes and have
different structures, functions and expression patterns
Importance is found in diversity- many human diseases
are associated with dysfunction of individual classes of
ion channels
Na+ LGC
K+ LGC
Vm -74
0
mV
What would happen to the
resting membrane potential if
these channels opened?
Cl- LGC
• The Excitatory Postsynaptic Potential (EPSP)
– Na+ ions rush to inside of membrane through ionophores opened by
transmitter.
– The increase in voltage above the normal resting potential (to a less
negative value is the excitatory postsynaptic potential.
– A single EPSP can be 0.5-1.0 mV (how many mV difference do we need
to reach threshold?
dendrite
Membrane is depolarized, more likely
to reach threshold
Na+: 142 mEq/L
14 mEq/L
K+ : 4.5 mEq/L
120 mEq/L
Cl- : 107 mEq/L
8 mEq/L
axon
-45mV
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• The Inhibitory Postsynaptic Potential (IPSP)
– Inhibitory synapses open K+ or Cl- channels and causes
hyperpolarization of the neuron. Making neuron less likely to reach
threshold
– Positively charged K+ ions moving to exterior make membrane
potential more negative than normal (hyperpolarizing).
– Negatively charged Cl- ions moving to interior make membrane
potential more negative than usual (hyperpolarizing).
Na+: 142 mEq/L
K+ : 4.5 mEq/L
14 mEq/L
120 mEq/L
Cl- : 107 mEq/L
8 mEq/L
axon
-90mV
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Whether a neuron “responds” or not,
depends on temporal and spatial summation
of EPSPs and IPSPs
These channels open and close rapidly providing a
means for rapid activation or rapid inhibition of
postsynaptic neurons.
1msec is needed for an action potential, but a graded
potential can last ~15msec. This means we can
“add” excitatory and inhibitory potentials
Temporal summation: same presynaptic neuron fires repeatedly
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Spatial summation- stimuli from two
different presynaptic neurons (different
locations)
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Disturbing an Excitable Cell
• Electrical stimulation (or even
mechanical stimulation) can
result in changes in voltage.
Depolarizing currents change
the voltage on the membrane,
bringing it toward threshold:
– If stimuli are sub-threshold,
the result is a local
potential
– If stimuli are threshold or
above threshold stimuli, the
result is an action potential
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What happens at threshold?
•
•
•
A temporary, short-lived membrane permeability
change. Membrane becomes 40 x more
permeable to Na+ than to K+, then quickly
returns to previous state
How?
Opening and closing of voltage-gated channels.
VGC (Voltage-gated channels): Open/close
depending on the voltage across the membrane
– Na+ VGC, K+ VGC, Ca++VGC
– Located on the axon, at hillock and beyond
• Can allow ions to move at high rates
• Allow ions to move down their EC
gradients
• Conductances are voltage dependent
• Threshold is the “trigger” that starts a
“dance of the gates”
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The action potential, dance of
the gates
• Upstroke
– Na+ permeability increases
– Membrane potential
approaches E Na+
• Downstroke
– Potassium permeability
increases
– Hyperpolarization occurs
due to increased K+
conductance from late
K+VGC closure
– Membrane potential
approaches E K+
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Ion channels – Activation,
Inactivation, deactivation
• Depolarization causes:

closed
Na channels to activate (open)
but it also causes inactivation


inactivated channels do not
pass any ions (non-conducting
state)
By contrast, most K channels
show activation and
deactivation but not
inactivation

inactivation
open
inactivated
The fall in current at the end is
deactivation (opposite of
activation)
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Copyright © 2006 by Elsevier, Inc.
Refractory Periods
mV
0
-40
Threshold
-80
0
1
Absolute
2
3
4
5 msec
Relative
ARP - due to voltage inactivation of Na channels
Refractory periods limit maximum frequency of APs
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Functions of action potentials
• Information delivery to CNS
 Transfers all sensory input to
CNS.
 The frequency of APs encodes
information (recall amplitude
cannot change).
• Rapid transmission over
distance (nerve cell APs)
 Note: speed depends on fiber size
and whether it is myelinated.
 In non-nervous tissue APs are the
initiators of a range of cellular
responses.
Muscle contraction
Figure 5-16; Guyton & Hall
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http://www.blackwellpublishing.com/
matthews/actionp.html
http://faculty.washington.edu/chudler/ap.html
Figure 5-17; Guyton & Hall
Saltatory Conduction
The AP is a passive event: ions diffuse down their EC gradients
when gated channels open.
A “wave of depolarization” occurs along the neighboring areas.
Occurs in one direction along the axon; actually, AP regenerates
over and over, at each point by diffusion of incoming Na+
….WHY?
Refractory period (Na+ channels become inactivated).
AP’s only occur at the nodes (Na channels concentrated here!)
 increased velocity
 energy conservation
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Conduction velocity
- non-myelinated vs myelinated -
non-myelinated
myelinated
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Multiple Sclerosis
- MS is an immune-mediated
inflammatory demyelinating
disease of the CNS - About 1 person per 1000 in
US is thought to have the
disease - The female-to-male
ratio is 2:1 - whites of northern
European descent have the
highest incidence
http://www.emedicine.com/pmr/topic82.htm
Copyright © 2006 by Elsevier, Inc.
Patients have a difficult time
describing their symptoms. Patients
may present with paresthesias of a
hand that resolves, followed in a
couple of months by weakness in a leg
or visual disturbances. Patients
frequently do not bring these
complaints to their doctors because
they resolve. Eventually, the resolution
of the neurologic deficits is incomplete
or their occurrence is too frequent, and
the diagnostic dilemma begins.
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• Structures important to the
function of the synapse:
– presynaptic vesicles
• contain neurotransmitter substances
to excite or inhibit postsynaptic
neuron
The Synapse
– mitochondria
• provide energy to synthesize
neurotransmitter
• Membrane depolarization by an
action potential causes emptying
of a small number of vesicles into
the synaptic cleft
• Presynaptic membranes contain
voltage - gated calcium channels.
VOCC
– depolarization of the presynaptic
membrane by an action potential
opens Ca2+ channels
Ca+2
2+
– influx of Ca induces the release of
the neurotransmitter substance
•Postsynaptic membrane contains receptor proteins for the
transmitter released from the presynaptic terminal.
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Synaptic Events-watch animation
• NTS release
• NTS diffuses across cleft
• Binds to receptors (LGC’s)
reversible binding
• Opens LGC (LGC’s are ion
selective) and diffusion of ions:
Influx or efflux
• Allowing depolarization or
hyperpolarization of cell body
• Result in graded voltage
changes, local potentials in
postsynaptic cell body
• If depolarizing, called EPSP
• If hyperpolarizing, called IPSP
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