signal conduction - graded and action potentials_l11-l12_sep 28 2015

© 2013 Pearson Education, Inc.

Neurons: Cellular and Network Properties

Chapter 8

Electrical Signals in Neurons

Review• 2 factors influence the membrane resting potential

– The uneven distribution of ions across the cell membrane– Different membrane permeability to those anions– Permeability: having gate to a particular ion – Responding to stimulus means gated channels, not talking about background

channels in resting potential

• The Nernst equation describes the membrane potential that would result if the membrane were permeable to only one ion.

Electrical Signals: GHK Equation

Goldman-Hodgkin-Katz equation: -Predicts membrane potential that results from the contribution of all ions that can cross the membrane-Determined as the combined contribution of each ion (concentration x permeability) to the membrane potential-Different from Nernst Eq., which calculates the equilibrium potential for a single ion


RT (at 37oC) 61 F

=

Permeability concentration

-Cl is diff because opposite charge-need to know diff between this and Nernst, apply equation, what is the purpose of it?

Nernst equilibrium potential

Kandel et al., Principles of Neural Science, 3rd. Ed

EK = RT ln [K+]outside ZF [K+]inside

E: Nernst equilibrium potentialR: gas constantT: temperature in KelvinZ: valence (charge)F: Faraday constantEK= -80 to -90 mV

Vm = EK

Single ion at electrochem equilibrium

Electrical Signals: Ion Movement• Resting membrane potential determined primarily by

– K+ (high permeability at rest)– Cell’s resting permeability to K+, Na+, and Cl–

• How does a cell changes its ion permeability?– Opening or closing ion channels (existing or new)– There are 4 main type of selective ions channels:

Na+ channelsK+ channelsCa2+ channelsCl- channels

– There are other channels that are less selective: •e.g. Cation non-selectiveligand gated channels that cause depolarization (ATP receptors, glutamate, serotonin)allow huge movement of positive ions, doesn’t care what types of ions, just want to depolarize


Electrical Signals: Ion Movement• Gated channels control ion permeability

– Mechanically gated: found in sensory neurons and open in response to physical forces, such as pressure or stretch.

– Chemically gated (or ligand gated): respond to ligands, such as neurotransmitters and neuromodulators.

– Voltage-gated: action potentials; respond to changes in membrane potential. Threshold voltage varies from one channel type to anotherneeds to

reach certain range to activate Activation: channels opening to allow ion flow Inactivation: channels close even though the stimulus is still present

need to inactivate or else cell will die from too much positive charge


Changes in Vm: depolarization vs hyperpolarization

Time (msec)

Resting membranepotential difference (Vm)

Vmdepolarizes Vm

hyperpolarizes

Mem

bran

e po

tent

ial (

mV)

20

20

60

100

0

Graded Potentials & Action PotentialsVoltages changes across the membrane can be classified into two basic types: graded potentials and action potentials

Graded potentials (GP) are variable-strength signals that travel over short distances and lose strength (decay) as they travel along the cell. They are use for short distance communication. If a GP is strong enough it generates an action potential.first response, change in resting membrane potentialtriggered by gated channels not involved in action potential

Action potentials (AP) are very brief, large depolarizations that travel for long distances through a neuro without losing strength. AP function is rapid signaling over long distances.

Graded Potentials

Figure 8.7

GP decrease in strength as they spread out from the point of origin.no insulation around cell body, so signal leaks out to surrounding channels, tissues, etc.

GP are amplitude (size) is directly proportional to the strength of the stimulus.

Generated by chemically gated (ligand gated) ion channels or by mechanically gated ion channelsNOT sodium potassium channels

-positive charges depolarize, but cell wants to bring it back to resting so positive charge leaves (decays)

Local current flow

Graded Potentials Reflect Stimulus Strength• Local current flow is a wave of depolarization that moves through the cell

• Graded potentials lose strength as they move through the cell due to– Current leak– Cytoplasmic resistanceforces that make it uncomfortable for ions to

come in so they just leave the cellpathway of least resistance

• Excitatory versus inhibitory- Depolarization: Excitatory Postsynaptic Potential (EPSP)- Hyperpolarization: Inhibitory Postsynaptic Potential (IPSP)shut down neurons, not for action potentialshut down noise so focus on necessary signal

• If strong enough (excitatory), graded potentials reach the trigger zone and fire an action potentialneed certain amplitude


Graded Potentials

Subthreshold not strong enough to cause action

Suprathreshold

Threshold: is the most negative voltage that must be achieved for firing of action potentials to occur (~ -53 mV, depending on the neuron).at trigger zone: membrane packed with voltage gated NaK channels

Figure 8.7Note: just through membrane of cell

Eg. Neuron need send signal to heart to stop freaking out

Action Potentials Travel Long Distances• APs are electrical signals of uniform strength that travel from a neuron’s

trigger zone to the end of its axon does not decay!

• Conduction is the high-speed movement of an action potential along an

axon

• All-or-none (different from graded potential)

– due to threshold

– The strength of the GP that initiates an AP has no influence on the

amplitude of the AP, just influence whether it happens or not

• There is no single AP that moves through the cell, rather a new AP is

generated in the adjacent area of the membrane (not continuous)


Figure 8.8

Conduction of an Action PotentialThe conduction of an action potential down an axon is similar to energy passed alonga series of falling dominos. In this snapshot, each domino is in a different phase of falling. In the axon,each section of membrane is in a different phase of the action potential.

A wave of electrical current passes down the axon.

Trigger zone

Direction of conduction

Action potential

Electrodes have beenplaced along the axon.

Membrane potentialsrecorded simultaneouslyfrom each electrode.

Time

Simultaneous recordings show that each section ofaxon is experiencing a different phase of the action potential.

Mem

bran

e po

tent

ial (

mV)

Parts of an Action Potential

ThresholdMem

bran

e po

tent

ial (

mV)

PNa

PNa

PK

PK

30

10

100

30

50

70

90

0 1 2 3 4

Resting membrane potential

Depolarizing stimulus

Membrane depolarizes to threshold.Voltage-gated Na and K

channels begin to open.

Rapid Na entry depolarizes cell.

Na channels close and slowerK channels open.

K moves from cell to extracellularfluid.

K channels remain open andadditional K leaves cell, hyperpolarizing it, wants to move closer to own potential.Voltage-gated K channels close,less K leaks out of the cell.Cell returns to resting ion permeabilityand resting membrane potential with background channels

1

2

3

4

5

6

7

8

9

Figure 8.9

Rising phase Repolarization phase

Peak

Rising phase caused by strong driving force of Na rushing in-K channels open later, slower response

NaV and KV channels

Slightly diff in diff parts of body

Ion permeability during an Action Potential

K

Na

Time (msec)

Ion

perm

eabi

lity

0 1 2 3 4

Voltage

Resting Rising Falling After-hyperpolarization Resting

Hyperpolarization: No PNa and high PK

Figure 8.10a

5570

300

mV

Na+

ICF

ECF

Inactivationgate

Activationgate

At the resting membrane potential, the activation gatecloses the channel.NaV gates very quick

Voltage-gated Na+ channel Action potential like language tween neuronshave to be clear, quick responses

Figure 8.10b (2 of 5)

5570

300

mV

Na+

Depolarizing stimulus arrives at the channel. At threshold, Activation gate opens.huge influx of sodium into cell

Voltage-gated Na+ channel

stimulus

Figure 8.11

ACTION POTENTIAL

Depolarization

Na+ entry during an actionpotential creates a positivefeedback loop. The positivefeedback loop stops whenthe Na + channel inactivationgates close.

Rising phase Falling phasePeak

Na+ enterscell

Na+ channelactivation gates

open rapidly

Moredepolarization

Slow K+ channels open

K+ leavescell Repolarization

triggers

Feedback cycle

To stop cycle,slower Na+ channel

inactivation gatecloses (see Fig. 8.10).

Positive Feedback

5570

300

mV

Na+

With activation gate open, Na+ enters the cell.


5570

300

mV

Na+

Inactivation gate closes at +30 and Na+ entry stops


INACTIVATION

5570

300

mV

Na+

During repolarization caused by K+ leaving the cell, the twogates reset to their original positions.hyperpolarization super important: allows deactivation gate to reset so another action potential can occur


Back to resting potential

Refractory period following an AP

Figure 8.12

All N

a ch

anne

l bei

ng u

sed All Na channels inactivated

Some Na channels are still inactivated

AP unidirectional, dendrite to end terminal, don’t go back to cell body

At peak, all Na channels inactivated or in use Less sodium channels ready to

fire againharder to get Na influx into cell, need more push

Summary: Graded Potential vs. AP

Table 8.3

Refractory period following an AP

Figure 8.12

All N

a ch

anne

l bei

ng u

sed All Na channels inactivated

Some Na channels are still inactivated

Nervous I: The Action Potential


Interactive Physiology® Animation: Nervous I: The Action Potential

Action Potentials are Conducted• AP are conducted for long distances (meters or more)

• The AP that reaches the end of the axon is identical to the AP that was

generated at the trigger zone

• GP: – The depolarization of a section of an axon causes positive current to

spread by local current flow, – Simultaneously, on the outside of the axon membrane current flows

back towards the depolarized section– Current flows dies out, unless there are Na and K channels

• AP:

– Generation and conductions, see fig. 8.14


Figure 8.14

A graded potential abovethreshold reaches thetrigger zone.

Trigger zone

Axon


1. A supra-thershold GP enters trigger zone

Figure 8.14


Trigger zone

Axon

Voltage-gated Na+ channelsopen, and Na+ enters the axon.

Na+


1. Graded potential enters trigger zone

2. Voltage-gated Na+ channels open, and Na+ enters axon

3. Positive charge spreads along adjacent sections of axon by local current flow

Figure 8.14


Trigger zone

Axon


Na+

Positive charge flows into adjacentsections of the axon by local current flow.





Figure 8.14


Trigger zone

Axon


Na+

Positive charge flows into adjacentsections of the axon by local current flow.





4. Local current flow causes new section of the membrane to depolarize

5. Loss of K+ repolarizes the membrane

6. The refractory period prevents backward conduction

Local current flow from theactive region causes new sectionsof the membrane to depolarize.

Na+

K+The refractory period prevents backwardconduction. Loss of K+ from thecytoplasm repolarizes the membrane.

Refractoryregion

Active region Inactive region

Electrical Signals: Speed of AP PropagationSpeed of action potential in neuron influenced by

1) Diameter of axon

- Larger axons are faster

2) Resistance of axon membrane to ion leakage out of the cell

- Myelinated axons are faster

- Saltatory conduction between nodes of Ranvier


Figure 8.15

Axon diameter: large axons offer less resistance

http://i.imgur.com/ke3YICu.gif

http://i.imgur.com/ke3YICu.gif

Action potentials appear to jump from one node of Ranvier to the next. Only the nodes have voltage-gated Na+ and K+ channels.

Myelin: saltatory conduction

Figure 8.16b

Why conduction is more rapid in salutatory conduction?- cable props. of the membrane- no requires channels opening in between nodes- only channels at the nodes

Figure 8.16b

In demyelinating diseases, conduction slows when current leaks out of the previously insulated regions between the nodes.

Demyelination

Nervous I: Propagation of an Action Potential


A&P FlixTM: Propagation of an Action Potential

Figure 8.17a (1 of 4)

Normal plasma [K+] is 3.5 – 5 mM.

Threshold

Stimulus

Time

Mem

bran

e po

tent

ial (

mV)

When blood K+ is in thenormal range (normokalemia),a subthreshold gradedpotential does not firean action potential.

55

70

0

Chemical factor can alter electrical activity- Neurotoxins: block voltage gated Na+ channels (e.g. tetrodotoxin (TTX), lidocaine)

- Alterations in extracellular ion concentrations (K+, Ca2+)

Example: increase in blood K+ conc. (Hyperkalemia)

Figure 8.17b (2 of 4)

Threshold

StimulusMem

bran

e po

tent

ial (

mV)

55

70

0

Normal plasma [K+] is 3.5 – 5 mM.

In normokalemia, asuprathreshold (above-threshold) stimulus willfire an action potential.

Figure 8.17c (3 of 4)

Threshold

Stimulus

55

70

0

Hyperkalemia depolarizes cells.

Hyperkalemia, increasedblood K+ concentration,brings the membrane closerto the threshold. Now astimulus that would normallybe subthreshold cantrigger an action potential.

- Hyperkalemia: increase in blood K+ conc.

- Shift resting potential closer to threshold, the cell fires APs in response to smaller graded potentials.

Threshold

Stimulus

55

70

0

Hypokalemia hyperpolarizes cells.

Hypokalemia, decreasedblood K+ concentration,hyperpolarizes the membraneand makes the neuron lesslikely to fire an actionpotential in response to astimulus that would normallybe above the threshold.

Figure 8.17d (4 of 4)

- Hypokalemia: decrease increase in blood K+ conc.

- Shift resting potential farther away from threshold (hyperpolarization), the cell will not fire APs in response to a normal stimulus.

signal conduction - graded and action potentials_l11-l12_sep 28 2015

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