Bio 111 Lecture 14
Action Potentials
Principal way neurons send signals
– Means of long-distance neural communication
• Occur only in muscle cells and axons of neurons
• Brief reversal of membrane potential with a change in voltage
of ~100 mV
• Action potentials (APs) do not decay over distance as graded potentials do
• In neurons, also referred to as a nerve impulse
• Involves opening of specific voltage-gated channels
Generating an Action Potential
Four main steps Step 1
1. Resting state: All gated Na+ and K+ channels are closed
• •
Only leakage channels for Na and K are open (RMR)
Each Na channel has two voltage-sensitive gates
- Activation gates: closed at rest; open with depolarization,
allowing Na to enter cell
- Inactivation gates: open at rest; block channel once it is open to
prevent more Na from entering cells
Each K+ channel has one voltage –sensitive gate
- Closed at rest
- Opens slowly with depolarization
Step 2
Depolarization: Na+ channels open
• Depolarizing local currents open voltage-gated Na+ channels, and Na+ rushes into cell
• Na+ activation and inactivation gates open
• Na+ influx causes more depolarization, which opens more Na+
channels, and, as a result, ICF becomes less negative
• At threshold (~-55 mV), positive feedback causes opening of all Na+
channels
- Results in large action potential spike - Membrane potential jumps to +30 mV
Step 3
Repolarization: Na+ channels are inactivating, and K+ channels open
• Na+ channel inactivation gates close
-Membrane permeability to Na+ declines to resting state -AP spike stops risin
• Voltage-gated K+ channels open
-K+ exits cell down its electrochemical gradient
• Repolarization: membrane
returns to resting membrane potential
Step 4
Hyperpolarization: Some K+ channels remain open, and Na+ channels reset
• Some K+ channels remain open, allowing excessive K+ efflux -Inside of membrane becomes more negative than in resting
state
• This causes hyperpolarization of the membrane (slight dip below
resting voltage)
• Na+ channels also begin to reset
Repolarization resets electrical conditions, not ionic conditions
• After repolarization, Na+/K+ ATP-ase pumps (thousands of them in an axon) restore ionic conditions
Required Reading
Focus Figure 11.2
Threshold and the All-or-None Phenomenon
Not all depolarization events produce APs
• For an axon to “fire,” depolarization must reach threshold voltage in
hillock area to trigger action potential
• At threshold (~-55 mV):
– Na+ permeability increases because voltage-gated Na+ channels open
– The positive feedback cycle begins
• All-or-None: AP either happens completely, or doesn’t happen at all
Propagation
allows AP to be transmitted from origin down entire axon length toward terminals
• Na+ influx through voltage gates in one membrane area cause local currents that cause opening of voltage gated Na+ channels in adjacent membrane areas
– Leads to depolarization of that area, which in turn causes depolarization in next area
Once initiated, an AP is self-propagating in forward direction
– In nonmyelinated axons, each successive segment of membrane
depolarizes, then repolarizes
– Propagation in myelinated axons differs
• Since Na+ channels closer to the AP origin are still inactivated, no
new AP is generated there
– AP occurs only in a forward direction
Coding for Stimulus Intensity
All action potentials are alike and are independent of stimulus intensity
• CNS tells difference between a weak stimulus and a strong one by frequency of impulses
– Frequency is number of impulses (APs) received per second
– Higher frequencies mean stronger
stimulus
Refractory Period
Time in which neuron can’t trigger another AP •Voltage-gated Na+ channels are open (or open but inactivated), so neuron can’t respond to another stimulus
Conduction Velocity
APs occur only in axons, not other cell areas
AP conduction velocities in axons vary widely Rate of AP propagation depends on two factors
Conduction Velocity Two Factors
Axon diameter
• Larger-diameter fibers have less resistance to local current flow, so have faster impulse conduction
Degree of myelination
• Two types of conduction depending on presence or absence of myelin
– Continuous conduction: slow conduction that occurs in nonmyelinated axons
– Saltatory conduction: occurs only in myelinated axons and is about 30 times faster
• Myelin sheaths insulate and prevent leakage of charge
• Voltage-gated Na+ channels located at myelin sheath gaps • APs generated only at gaps
• Electrical signal appears to jump rapidly from gap to gap
Homeostatic Imbalance 11.2: Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease that affects primarily young adults
• Symptoms: visual disturbances, weakness, loss of muscular control, speech disturbances, incontinence
• Treatment: drugs that modify immune system activity
The Synapse
Nervous system works because information flows from neuron to neuron
Neurons are functionally connected by synapses, junctions that mediate information transfer
– From one neuron to another neuron
– Or from one neuron to an effector cell
Presynaptic neuron
neuron conducting AP down axon toward
synapse (sends information)
Postsynaptic neuron
neuron transmitting AP (if hillock reaches threshold) away from synapse (receives information)
– In peripheral nervous system may be a neuron, muscle cell, or gland cell
Most function as both – part of a chain or network of neurons
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Synaptic connections
– Axodendritic: between axon terminals of one neuron and
dendrites of others
– Axosomatic: between axon terminals of one neuron and soma (cell body) of others
Less Common Synaptic connections
• Axoaxonal (axon to axon)
• Dendrodendritic (dendrite to dendrite) • Somatodendritic (dendrite to soma)
Two main types of Synapses
Chemical synapse
Electrical synapse
Chemical Synapses
Most common type of synapse
• Specialized for release and reception of chemical
neurotransmitters
• Typically composed of two parts
– Axon terminal of presynaptic neuron: contains synaptic
vesicles filled with neurotransmitter
– Receptor region on postsynaptic neuron’s membrane:
receives neurotransmitter
• Usually on dendrite or cell body
– Two parts separated by fluid-filled synaptic cleft
• Electrical impulse changed to chemical across synapse, then back into electrical
Chemical Synapses
Transmission across synaptic cleft
Synaptic cleft prevents nerve impulses from directly passing
from one neuron to next
– Depends on release, diffusion, and receptor binding of neurotransmitters
– Ensures unidirectional communication between neurons
Synaptic Delay
Time needed for neurotransmitter to be released, diffuse across synapse, and bind to receptors
• Can take anywhere from 0.3 to 5.0 ms
– Synaptic delay is rate-limiting step of neural transmission
• Transmission of AP down axon can be very quick, but synapse slows down transmission to postsynaptic neuron significantly
• Not noticeable, because these are still very fast
Study pg
#7
Steps of Chemical Synapses
1. AP arrives at Axon Terminal
2. Voltage-gated Ca++
channels open, Ca++
enters axon
3. Ca++ induces synaptic
vesicles to release neurotransmitter by exocytoses
4. Neurotransmitter diffuses across synaptic cleft to bind on receptors on target cell
5. Ion channels open in target cell
6. Neurotransmitter is broken down
A&P
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terminal
Electrical Synapses
Less common than chemical synapses
• Neurons are electrically coupled
– Joined by gap junctions that connect cytoplasm of adjacent neurons
– Communication is very rapid and may be unidirectional or bidirectional
– Found in some brain regions responsible for eye movements or hippocampus in areas involved in emotions and memory
– Most abundant in embryonic nervous tissue
Postsynaptic Potentials
Neurotransmitter receptors cause graded potentials that vary in strength based on:
– Amount of neurotransmitter released
– Time neurotransmitter stays in cleft
• there are two types of postsynaptic potentials
There are two types of postsynaptic potentials
EPSP: excitatory postsynaptic potentials
• Neurotransmitter binding opens chemically gated channels
– Allows simultaneous flow of Na+ and K+ in opposite directions
• Na+ influx greater than K+ efflux, resulting in local net graded potential depolarization called excitatory postsynaptic potential (EPSP)
• EPSPs trigger AP if EPSP is of sufficient strength to spread a membrane depolarization to the axon hillock that reaches threshold (-55 mV)
Inhibitory Synapses and IPSPs
• Neurotransmitter binding to receptor opens chemically gated channels that allow entrance/exit of ions that cause hyperpolarization
– Makes postsynaptic membrane more permeable to K+ or Cl–
• If K+ channels open, it moves out of cell
• If Cl– channels open, it moves into cell
– Reduces postsynaptic neuron’s ability to produce an action
potential
• Moves neuron farther away from threshold (makes it more negative)
Look at pg
24
Integration and Modification of Synaptic Events
Summation by the postsynaptic neuron
– A single EPSP cannot induce an AP, but EPSPs can summate (add together) to influence postsynaptic neuron
• IPSPs can also summate
– Most neurons receive both excitatory and inhibitory inputs
from thousands of other neurons
• Only if EPSPs predominate and bring axon hillock to threshold (-55mV) will an AP be generated in the post- synaptic neuron
Neurotransmitters
Language of nervous system
• 50 or more neurotransmitters have been identified
• Most neurons make two or more neurotransmitters
– Neurons can exert several influences
• Usually released at different stimulation frequencies
• Classified by:
– Chemical structure
– Function
Classification of Neurotransmitters by Chemical Structure
Acetylcholine (ACh)
– First identified and best understood, acetic acid and choline – Released at neuromuscular junctions
• Also used by many ANS neurons and some CNS neurons – Degraded by enzyme acetylcholinesterase (AChE)
Biogenic amines
– Catecholamines
Dopamine, norepinephrine (NE), and epinephrine: made from the amino acid tyrosine
Indolamines
Serotonin: made from the amino acid tryptophan
Histamine: made from the amino acid histidine
– All widely used in brain: play roles in emotional behaviors and biological clock
– Used by some ANS motor neurons especially NE
– Imbalances are associated with mental illness
Neurotransmitters exhibit a great diversity of functions
Functions can be grouped into two classifications
– Effects – Actions
Effects: excitatory versus inhibitory
– Neurotransmitter effects can be excitatory (depolarizing)
and/or inhibitory (hyperpolarizing)
– Effect determined by receptor to which it binds
§ GABA and glycine are usually inhibitory
§ Glutamate is usually excitatory
§ Acetylcholine and NE bind to at least two receptor types with opposite effects
– ACh is excitatory at neuromuscular junctions in skeletal muscle
– ACh is inhibitory in cardiac muscle
Neuromodulator
chemical messenger released by neuron that does not directly cause EPSPs or IPSPs but instead affects the strength of synaptic transmission
§ May influence synthesis, release, degradation, or reuptake of neurotransmitter
§ May alter sensitivity of the postsynaptic membrane to neurotransmitter.
§ May be released as a paracrine – Effect is only local
Neurotransmitter Actions: direct versus indirect
– Direct action: neurotransmitter binds directly to and opens
ion channels
• Promotes rapid responses by altering membrane potential
• Examples: ACh and amino acids
– Indirect action: neurotransmitter acts through intracellular
second messengers, usually G protein pathways
• Broader, longer-lasting effects similar to hormones
• Biogenic amines, neuropeptides, and dissolved gases
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 that causes
hyperpolarization (DIRECT)
G protein–linked receptors
– Responses are indirect, complex, slow, and often prolonged – Involves transmembrane protein complexes
– Cause widespread metabolic changes
– Examples:
Muscarinic (autonomic NS) ACh receptors § Receptors that bind biogenic amines
Receptors that bind neuropeptides (INDIRECT)
Neuropathy
Peripheral neuropathy happens when the nerves that are located outside of the brain and spinal cord (peripheral nerves) are damaged. This condition often causes weakness, numbness and pain, usually in the hands and feet.
Neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue. Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue.
Rabies
Rabies is a vaccine-preventable, zoonotic, viral disease affecting the central nervous system. Once clinical symptoms appear, rabies is virtually 100% fatal. In up to 99% of cases, domestic dogs are responsible for rabies virus transmission to humans.
Shingles
Shingles (herpes zoster) is a viral infection that causes an outbreak of a painful rash or blisters on the skin. It's caused by the varicella-zoster virus, which is the same virus that causes chickenpox. The rash most often appears as a band of rashes or blisters in one area of your body.