Second Half of Chapter 13 in Becker et al 6th edition
E. The Action Potential
1. coordinated opening/closing of ion channels
leads to the action potential
2. 1930's--discovery of giant axons in squid
a, squid axons not myelinated
b. conduction velocity directly proportional
to axon diameter (Note: myelination
in animal nerves allows rapid impulses
w/o increase in diameter)
c. want all muscles in mantle to contract same time
- these axons stimulate the explosive expulsion of
water from mantle cavity in squid
d. axons leading to furthest part mantle must be large
e. can get HUGE axon diameter = 0.5 to 1.0 mm
f. allows EASY insertion of microelectrodes
-cartoon of measuring membrane potential
g. ALSO allows insertion of a 2nd electrode
-2nd electrode allows the researcher
to suddenly change the membrane
potential locally
-researcher can "trigger" what happens
-can make membrane potential more
positive => depolarize membrane
by any amount
-eg: go from -60 mV to -50 mV
-eg: go from -60 mV to -40 mV
-eg: go from -60 mV to -30 mv
-can make membrane potential more
negative => hyperpolarize membrane
-eg: go from -60 mV to -80 mV
-usually researchers depolarize the membrane
-after a subthreshold (small => less than 20 mV)
depolarization membrane potential
just returns to resting state at about -60 mV
-if a depolarization is large enough to reach a
threshold potential, an action potential begins
3. Action Potential = very brief but large
electrical depolarization AND
repolarization of neuron membrane that
proceeds down an axon in a wave
a. measured with apparatus above
-see a graphic action potential
b. action potential caused by:
(1) sudden inward movement of Na+ ions
-Na+ channels open fast
-Na+ follows its concentration gradient
-Na+ attracted to inside negative
membrane potential
-after the appropriate number of Na+ ions
have entered, the Na+ channel becomes inactive
(2) subsequent outward movement K+ ions
-triggering mechanism of K+ channels causes them to open more slowly
-K+ movement lags behind Na+ entry
-Na+ ion entry dissipates the
potential that once kept K+ in
-now K+ free to rush out of cell
-driven by:
-K+ diffuses down its concentration gradient
-membrane potential (inside positive) due to Na+ ions
-after the appropriate number of K+ ions
have left, the K+ channel becomes inactive
(3) meanwhile, Na/K pump just keeps
pumping, thus restoring the Na out & K in concentration
gradient soon after the Na and K channels
become inactive thus redeveloping
the resting potential
c. once an action potential is initiated in one region of
a neuron, a depolarization "wave" spreads out
sequentially to the rest of the neuron = propagation
(1) see a simplified animation of an action potential
propagation
4. Phases of the Action Potential
a. resting phase
(1) membrane potential poised
at -60 mV inside negative
(2) voltage dependent Na+ and
K+ channels closed
(3) K+ channels 100x more leaky
than Na+ channels in resting phase
(4) the negative membrane potential helps
keep K+ ions inside or very close to
outside of the cell even though there is
a large concentration gradient and
a leaky K+ channel
(5) consider subthreshold depolarization
-small depolarizations (less than 20 mV)
-sm. depolarizations trigger A FEW voltage
gated Na+ channels to open
-Na+ comes in open channels
-incoming Na+ FURTHER reduces the
membrane potential
- further reduction in membrane potential
leads to more open Na+ channels
-chain reaction starts
-without the K+ channels, this would lead
to complete depolarization
-BUT, with subthreshold depolarizations the Na+
influx starts slowly
-recall: only "a few Na+ channels open"
-recall: "incoming Na+ further reduces the
membrane potential"
-recall: K+ more leaky than Na+
-recall: K+ leakage restrained by
membrane potential
-SO: as membrane depolarizes,
K+ leaks out faster and prevents
further depolarization of membrane potential
(one Na+ in balanced by one K+ out = no net
change in potential)
-faster K+ leakage is possible because the
restraint on K+ leakage is reduced by
the inflowing Na+
-at -60 mV the K+ is held more tightly
-at -50 mV (some Na+ has rushed in) the K+
is not held as tightly and
more K+ leaks out faster down its large
concentration gradient preventing
further change in overall membrane potential
-at -40 mV (even more Na+ has rushed in) the
K+ is not held as tightly and even
more K+ leaks out even faster down its large
concentration gradient
(eg: 400 mM inside vs 20 mM outside)
preventing further change in
overall membrane potential
-SO: K+ leakage prevents the small
depolarizations from producing a
full scale chain reaction of Na+ channel opening
and the resulting action potential
(6) threshold depolarization
-discussed below as part of "depolarizing phase"
b. depolarizing phase
(1) consider a threshold depolarization
- larger depolarizations (greater than 20 mV)
cause many more Na+ channels to open
-K+ channels open later and more slowly
- flow of Na+ into the cell is faster than the
back leaking K+ can compensate for
- leads to greater depolarization
- leads to more open Na+ channels
- get a full chain reaction
- leads to 100% open Na+ channels
- Na+ rushes in until the membrane potential
becomes so positive that it causes the Na+
channels to become inactive (functionally closed)
-NOTE: full Na+ equilibrium
in about 1 millisecond!!!!!!
- get the peak (+40 mV) of the action potential
(2) see the ion fluxes
c. repolarizing phase
(1) Na+ channels remain inactive (functionally closed) until
membrane potential becomes negative and hyperpolarizes
(2) Large depolarization due to incoming Na+ causes voltage gated
K+ channels to become 100% open
-K+ rushes out through the channel
-(BOTH inside + memb. pot. & conc. grad. "push"
the K+ out of cell)
-Note: this is not the "leakage" discusses above
this is wide open K+ channels
(3) as K+ rushes out, the membrane potential repolarizes
-when there is one Na+ in for one K+ out then the
membrane potential will be back at -60 mV
d. hyperpolarizing phase
(1) But, K+ channels stay wide open longer and
the repolarization OVERSHOOTS the
resting potential point
(2) as the membrane potential passes the
resting potential, the K+ channels close
and become inactive
(3) But, K+ has been driven out by both
membrane potential and [ K+ ] gradient
(4) So, more K+ leaves then is minimally
required to satisfy the resting potential
(5) leads to hyperpolarization
(6) now both Na+ and K+ channels are inactive and closed
(7) Na/K pump keeps pumping out 3 Na+ and in 2 K+
-NOTE: the Na/K pump continues
pumping all the time
(8) membrane potential returns to resting potential at -60 mV
-driven by the Na/K pump
e. refractory phase
(1) after an action potential the channels
of the neuron are inactive
(2) period of inactivity lasts a few milliseconds
(3) inactive channels can't be triggered to open
(4) Na+ channels are inactive and closed and unable
to be triggered to open to allow transport Na+
-depolarization during refractory period
DOES NOT trigger channel opening
5. action potential propagation
a. two types of depolarizations
(1) passive spread of depolarization
-occurs in the dendrites and cell body
-dendrites and cell body have
different kinds of channels than do axons
-dendrites and cell body have
different kinds of channels based on the nerve cell type
-ligand gated channels (synapses)
-gap junctions
-temperature gated channels
-mechano gated channels
-BUT VERY FEW voltage gated channels
-POSSIBLE EXAM QUESTIONS:
-nerve membrane polarized
-depolarization starts when one of various channels opens
-Na+ rushes in and depolarization occurs locally
-local depolarization allows K+ to diffuse toward
regions of more negative membrane potential
at the cell body
-the [K+] is much greater locally than the [Na+]
-any given wave of K+ mediated depolarization
WEAKENS as the wave spreads out
from site of stimulous
-passive depolarizations can't
travel long distances
-starting a full blown action potential down the axon usually requires
multiple simultaneous incoming signals
such that the passive depolarization gets
large enough to trigger an action potential
at the axon hillock
-passive depolarization reaches the
axon hillock
-voltage gated channels (Na+ and K+) are very
abundant at the axon hillock and along the axon
- many Na+ channels are especially
concentrated at the axon hillock
-when a large passive depolarization
reaches the axon hillock the passive
depolarization triggers the voltage gated channels
of the axon hillock to open
-many hillock channels => rapid and large depolarization
-depolarization spreads down axon
-as long as the passive depolarization remains
above the threshold level the axon hillock will
keep sending periodic action potentials down the axon
(2) action potential propagation (nonmyelinated)
-see Fig 9-17
-axon polarized with a resting potential
-inside 60 mV negative
-axon has a long string of channels
-consider four points (P, Q, R & S) along axon
-action potential is stimulated at P
-Na+ rushes in and an inside
positive potential develops
-K+ & Na+ ions move toward closest region
with negative potential
-this is the immediately adjacent area
that has not been depolarized
-as Na+ ions move, adjacent areas become
depolarized
-when Q is depolarized to its threshold level
the action potential starts at Q
-meanwhile, P starts to recover
-K+ channels open
-K+ ions flow out
-resting potential returns
-action potential at Q stimulates
depolarization at R
-can't go back to P because
Na+ channels still in refractory phase
-Q recovers, and R stimulates
action potential at S
(3) rate of action potential propagation
(a) How fast does the action potential
move down the axon?
-fast pain neurons
-widespread in skin and a few internal
tissues (periosteum, arterial walls,
joint surfaces)
-other deep tissues have few fast pain neurons
-give rise to sharp pain, pricking pain, acute pain, electric pain
-triggered by suddent mechanical or thermal trauma
(knife cuts, needle pricks, electric shock, burning heat)
- action potential moves at 30 m/sec
-slow pain neurons
-slow burning pain, aching pain, throbbing pain
-more widely spread than fast pain neurons
-tend to respond to chemical stimuli related
to tissue damage
- action potential moves at 0.5 to 2 m/sec
(b) rate depends on electrical properties
of axon PM and cytoplasm
- cytoplasmic electrical resistance
to current flow
- how easily do ions move laterally
in cytosol?
- large neurons (eg: squid) have low
resistance => ion currents fast => impulses
go fast
- small neurons have higher resistance
=> ion currents slower => impulses slower
-capacitance of plasma membrane
-related to the numbers of + and - ions
on opposite sides of membrane
-as the resting potential develops,
positive ions accumulate on the
outside of membrane and negative ions
accumulate on inside
- accumulation due to electrostatic attraction
- electrostatic repulsion limits extent
- get locally higher [ion] on both sides membrane
- get electrostatic attraction between + and - ions
- both conditions FAVOR rapid
movement of ions when channels open
-with large capacitance can get a strong
depolarization
-BUT, the greater the capacitance, the slower
the impulse
-more negative charges close to PM
on the inside of the membrane
mean that more Na+ ions must come
in to neutralize the negative charges
and reduce the membrane potential
-more Na+ ion movement takes longer,
slows spread of depolarization
(c) rate depends on myelination of axon
-recall: Schwann cells and EM of myelin sheath
-some axons surrounded by myelin sheath
-supporting cells (eg: Schwann cells) wrap layers of their own
PM around the axon
-each supporting cell surrounds about
1 mm of axon
-many supporting cells required to cover whole axon
-sheath forms an insulating layer
(d) myelination DECREASES capacitance
- number on ions between axon and
supporting cells is controlled
(e) all channels found in the Nodes of Ranvier
(f) see sequence of events
-resting
-depolarized
-propagation
-movement of + charge
-positive charge moves much
faster than a Na+ or K+ can move
because what has really moved
is the ABSENCE of an electron
-don't need to physically move
a positively charged Na+ or K+
(g) impulses can move faster
due to saltatory propagation
(h) What happens when the
myelin sheath is damaged?
-multiple sclerosis
-myelin sheaths in CNS are
degraded due to unknown cause
-rate of action potential propagation
greatly slowed
-symptoms: fatigue, tingling, numbness,
painful sensations, blurred or double vision,
muscle weakness, impaired balance,
spasticity, tremor, changes in bladder, bowel,
and sexual function, cognitive changes such as
forgetfulness or difficulty concentrating, speech
and swallowing problems, and mood swings
F. Synaptic Transmission
1. synapse = a communicating junction
between a nerve and another cell
2. two types of synapses
a. electrical synapse between two neurons
(1) presynaptic neuron
(2) postsynaptic neuron
(3) presynaptic neuron connected to
dendrites of postsynaptic neuron
by gap junctions
(4) gap junctions allow ions to move
back and forth, another view
-depolorization spreads from one
cell to next by ion flow
through gap junctions
-critically important in cardiac muscle
-cardiac cells communicate
electrically through gap junctions
.
b. chemical synapse
(1) E.M. of chemical synapse
(1) presynaptic and postsynaptic neurons
are close but not connected
(2) gap about 20-50 nm = 0.02-0.05 um wide
- gap about 3 to 6 membrane thicknesses wide
(3) arrival of action potential triggers
release of neurotransmitter molecules
into the gap between neurons
(a) neurotransmitters stored in
synaptic vesicles just under
PM of neuron
(b) an action potential allows
voltage gated Ca+2 channels to open
-Ca+2 channels are found
only at the synapses
(c) Ca+2 rushes into the cytoplasm
-recall: [Ca+2] in cytoplasm very low
(d) increased [Ca+2] allows
synaptic vesicles to fuse with
PM and dump contents
(neurotransmitters such as acetylcholine)
outside of cell and into the gap
(4) neurotransmitters diffuse across gap
(5) neurotransmitters are bound by
postsynaptic neuron receptors
(a) eg: acetylcholine receptor = a ligand-gated Na+ channel
(b) two molecules of acetylcholine bind
to receptor and channel opens
-Na+ rushes in
(c) open channels lead to depolarization of
postsynaptic neuron
(d) action potential continues on in post
synaptic neuron
.
Ion Concentrations in Mammalian Cells and Blood Serum
| Ion | Cytoplasm (mM) | Blood Serum (mM) |
| K+ | 140 | 4 |
| Na+ | 12 | 145 |
| Cl- | 4 | 116 |
| HCO3- | 12 | 29 |
| protein neg charges | 138 | 9 |
| Mg+2 | 0.8 | 1.5 |
| Ca+2 | <0.0002 | 1.8 |
Back to the outline
.
Ion Concentrations in Squid Axons and Mammalian Neurons
| Squid Axons | Squid Axons | Mammalian Neuron | Mammalian Neuron |
| Ion | Outside (mM) | Cytoplasm (mM) | Outside (mM) | Cytoplasm (mM) |
| Na+ | 440 | 50 | 145 | 10 |
| Cl- | 560 | 50 | 125 | 10 |
| K+ | 20 | 400 | 5 | 140 |
Back to the outline
.
Hydration Numbers & Hydrated Radii of Ions
| Ion | Hydration Number
(H2O per Ion) | Hydrated Radius |
| Cs+ | 6 | 228 |
| K+ | 7 | 232 |
| Na+ | 13 | 276 |
| Li+ | 22 | 340 |
| Ba+2 | 28 | |
| Sr+2 | 29 | |
| Ca+2 | 29 | |
| Mg+2 | 36 | |
| Cd+2 | 39 | |
| Zn+2 | 44 | |
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