Download Gated Channels

Functions of the Nervous System
Sensory input
Integration
Motor output
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Figure 11.1
Neurons (Nerve Cells)
• Special characteristics:
•
•
•
•
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Long-lived ( 100
years or more)
Amitotic—with SOME
exceptions
High metabolic rate—
depends on continuous
supply of oxygen and
glucose
Plasma membrane
functions in:
• Electrical signaling
• Cell-to-cell
interactions during
development
White Matter and Gray Matter
• White matter
• Dense collections of
myelinated fibers
• Gray matter
• Mostly neuron cell
bodies and
unmyelinated fibers
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Structural Classification of Neurons
1.
2.
Multipolar—1 axon and several dendrites
•
Most abundant
•
Motor neurons and interneurons
Bipolar—1 axon and 1 dendrite
•
3.
Rare, e.g., retinal neurons
Unipolar (pseudounipolar)—single, short process that has two branches:
•
Peripheral process—more distal branch, often associated with a sensory
receptor
•
Central process—branch entering the CNS
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Functional Classification of Neurons
1. Sensory (afferent)
•
Transmit impulses from sensory receptors toward the CNS
2. Motor (efferent)
•
Carry impulses from the CNS to effectors
3. Interneurons (association neurons)
•
Shuttle signals through CNS pathways; most are entirely
within the CNS
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Role of Membrane Ion Channels
•
Two main types of ion channels
1.
Leakage (nongated) channels—always open
2.
Gated channels (three types):
•
Chemically gated (ligand-gated) channels—open with binding of a
specific neurotransmitter
•
Voltage-gated channels—open and close in response to changes in
membrane potential
•
Mechanically gated channels—open and close in response to physical
deformation of receptors
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Gated Channels
• When gated channels are open:
• Ions diffuse quickly across the membrane
along their electrochemical gradients
• Along chemical concentration gradients
from higher concentration to lower
concentration
• Along electrical gradients toward
opposite electrical charge
• Ion flow creates an electrical current and
voltage changes across the membrane
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Resting Membrane Potential (Vr) movie rmp
• Potential difference
across the membrane
of a resting cell
• Approximately –70 mV in
neurons (cytoplasmic
side of membrane is
negatively charged
relative to outside)
• Generated by:
• Differences in ionic
makeup of ICF and ECF
• Differential permeability
of the plasma membrane
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Resting Membrane Potential
• Differences in ionic makeup
•
ICF has lower concentration of Na+
and Cl– than ECF
•
ICF has higher concentration of K+
and negatively charged proteins (A–)
than ECF
• Differential permeability of
membrane
•
Impermeable to A–
•
Slightly permeable to Na+ (through
leakage channels)
•
75 times more permeable to K+ (more
leakage channels)
•
Freely permeable to Cl–
• Negative interior of the cell is due to
much greater diffusion of K+ out of
the cell than Na+ diffusion into the
cell
• Sodium-potassium pump stabilizes
the resting membrane potential by
maintaining the concentration
gradients for Na+ and K+
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Figure 11.7
The concentrations of Na+ and K+ on each side of the membrane are different.
Outside cell
The Na+ concentration
is higher outside the
cell.
K+
(5 mM )
Na+
(140 mM )
The K+ concentration
is higher inside the
cell.
K+
(140 mM )
Na+
(15 mM )
Inside cell
The permeabilities of Na+ and K+ across the
membrane are different.
Suppose a cell has only K+ channels...
K+ loss through abundant leakage
channels establishes a negative
membrane potential.
K+ leakage channels
K+
K+
K+
K+
K+
K+
Na+
K
K+
Na+
K+
K+
Na+
K+
K+
Na+
Cell interior
–90 mV
Now, let’s add some Na+ channels to our cell...
Na+ entry through leakage channels reduces
the negative membrane potential slightly.
Cell interior
–70 mV
Na+-K+ pump
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Na+-K+ ATPases (pumps)
maintain the concentration
gradients of Na+ and K+
across the membrane.
Cell interior
–70 mV
Finally, let’s add a pump to compensate
for leaking ions.
Na+-K+ ATPases (pumps) maintain the
concentration gradients, resulting in the
resting membrane potential.
Figure 11.8
Changes in Membrane Potential
• Depolarization
• Hyperpolarization
•
A reduction in membrane
potential (toward zero)
•
An increase in membrane
potential (away from zero)
•
Inside of the membrane
becomes less negative than
the resting potential
•
Inside of the membrane becomes
more negative than the resting
potential
•
Increases the probability of
producing a nerve impulse
•
Reduces the probability of
producing a nerve impulse
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Threshold
• At threshold:
• Membrane is depolarized by 15 to 20 mV
• Na+ permeability increases
• Na influx exceeds K+ efflux
• The positive feedback cycle begins
• Subthreshold stimulus—weak local depolarization that does
not reach threshold
• Threshold stimulus—strong enough to push the membrane
potential toward and beyond threshold
• AP is an all-or-none phenomenon—action potentials either
happen completely, or not at all
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Absolute Refractory Period
• Time from the
opening of the
Na+ channels
until the
resetting of the
channels
• Ensures that
each AP is an
all-or-none
event
• Enforces oneway
transmission of
nerve impulses
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Conduction Velocity
• Conduction velocities of neurons vary widely
• Effect of axon diameter
• Larger diameter fibers have less resistance to local current
flow and have faster impulse conduction
• Effect of myelination
• Continuous conduction in unmyelinated axons is slower
than saltatory conduction in myelinated axons
• Effects of myelination
• Myelin sheaths insulate and prevent leakage of charge
• Saltatory conduction in myelinated axons is about
30 times faster
• Voltage-gated Na+ channels are located at the nodes
• APs appear to jump rapidly from node to node
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Stimulus
Size of voltage
(a) In a bare plasma membrane (without voltage-gated
channels), as on a dendrite, voltage decays because
current leaks across the membrane.
Voltage-gated
Stimulus
ion channel
(b) In an unmyelinated axon, voltage-gated Na+ and K+
channels regenerate the action potential at each point
along the axon, so voltage does not decay. Conduction
is slow because movements of ions and of the gates
of channel proteins take time and must occur before
voltage regeneration occurs.
Stimulus
Myelin
sheath
(c) In a myelinated axon, myelin keeps current in axons
(voltage doesn’t decay much). APs are generated only
in the nodes of Ranvier and appear to jump rapidly
from node to node.
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Node of Ranvier
1 mm
Myelin sheath
Saltatory Conduction
Figure 11.15
Multiple Sclerosis (MS)
• An autoimmune disease that
mainly affects young adults
• Shunting and short-circuiting of
nerve impulses occurs
• Impulse conduction slows and
eventually ceases
• TX: Some immune system–
modifying drugs, including
interferons and Copazone:
• Hold symptoms at bay
• Reduce complications
• Reduce disability
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Nerve Fiber Classification
• Nerve fibers are classified
according to:
• Diameter
• Degree of myelination
• Speed of conduction
• Group A fibers
• Large diameter, myelinated
somatic sensory and motor
fibers
• Group B fibers
• Intermediate diameter, lightly
myelinated ANS fibers
• Group C fibers
• Smallest diameter,
unmyelinated ANS fibers
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A
B
C
**
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Figure 11.17, step 4
Ion movement
Graded potential
5 Binding of neurotransmitter
opens ion channels, resulting in
graded potentials.
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Figure 11.17, step 5
Enzymatic
degradation
Reuptake
Diffusion away
from synapse
6 Neurotransmitter effects are terminated
by reuptake through transport proteins,
enzymatic degradation, or diffusion away
from the synapse.
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Figure 11.17, step 6
Chemical Classes of Neurotransmitters movie
• Acetylcholine (Ach)
•
Released at neuromuscular
junctions and some ANS
neurons
•
Synthesized by enzyme
choline acetyltransferase
•
Degraded by the enzyme
acetylcholinesterase (AChE)
• Biogenic amines include:
• Catecholamines
• Dopamine,
norepinephrine (NE),
and epinephrine
• Indolamines
• Serotonin and
histamine
• Amino acids include:
• GABA—Gamma ()aminobutyric acid
• Glycine
• Aspartate
• Glutamate
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Chemical Classes of Neurotransmitters
• Peptides (neuropeptides) include:
•
Substance P
•
•
Endorphins
•
•
Mediator of pain signals
Act as natural opiates; reduce pain
perception
Gut-brain peptides
•
Somatostatin and cholecystokinin
• Purines such as ATP:
•
Act in both the CNS and PNS
•
Produce fast or slow responses
•
Induce Ca2+ influx in astrocytes
•
Provoke pain sensation
• Gases and lipids
•
Nitric oxide (NO)
•
Synthesized on demand
•
Activates the intracellular receptor guanylyl
cyclase to cyclic GMP
•
Involved in learning and memory
•
Carbon monoxide (CO) is a regulator of cGMP in the
brain
•
Endocannabinoids
•
Lipid soluble; synthesized on demand from
membrane lipids
•
Bind with G protein–coupled receptors in the
brain
•
Involved in learning and memory
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Neurotransmitter Receptors
•
Channel-linked receptors
• Ligand-gated ion channels
• Action is immediate and brief
• Excitatory receptors are channels for small cations
• Na+ influx contributes most to depolarization
• Inhibitory receptors allow Cl– influx or K+ efflux that causes hyperpolarization
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Neurotransmitter Receptors
•
G protein-linked receptors
•
Transmembrane protein complexes
•
Responses are indirect, slow, complex, and often prolonged and widespread
•
Examples: muscarinic ACh receptors and those that bind biogenic amines and neuropeptides
•
Neurotransmitter binds to G protein–linked receptor
•
G protein is activated
•
Activated G protein controls production of second messengers, e.g., cyclic AMP, cyclic GMP,
diacylglycerol or Ca2+Second messengers
•
Open or close ion channels
•
Activate kinase enzymes
•
Phosphorylate channel proteins
•
Activate genes and induce protein synthesis
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Stimulus
1 Receptor
Interneuron
2 Sensory neuron
3 Integration center
4 Motor neuron
5 Effector
Spinal cord (CNS)
Response
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Figure 11.23