Resting membrane potential ~ -70mV - Membrane is polarized

Resting membrane potential ~ -70mV - Membrane is polarized

(ie) Electrical charge on the outside of the membrane is positive while the electrical charge on the inside of the

membrane is negative

Depolarization: Inside of cell becomes less negative relative to outside (> –70 mV)

Hyperpolarization: Inside of cell becomes more negative relative to outside (< –70 mV)

Graded potentials: Localized changes in membrane potential (either depolarization or hyperpolarization) - (eg) A change in membrane potential from -70 to -60mV

= a 10 mV graded potential

Changes in membrane potential: Terminology

Action potentials: Rapid, substantial depolarization of the membrane (–70 mV to +30 mV to –70 mV all in 1 ms)

- Signal over long distances

Repolarization: Membrane returns to the resting potential (–70 mV) after depolarization

Direction of Impulse

The Structure of a Neuron

Nerve Impulse: An electrical charge that passes from one neuron

to the next,and finally to an end organ, such as a group of muscle fibers

Nerve impulse is generated here

RESTING STATE

Resting state

An action potential

Serve as electrical signals in excitable tissues

Action potential

Starts as a graded potential (Small localised change in membrane potential)

Requires depolarization greater than the threshold value: 15-20 mV

Once threshold is met or exceeded, the all-or-none principle applies

The strength of stimulus is not coded by the amplitude of the AP, but by the frequency.

- When a greater stimulus strength is applied to a neuron identical AP’s are produced more frequently.

Action potential

Starts as a graded potential (Small localised change in membrane potential)

Requires depolarization greater than the threshold value: 15-20 mV

Once threshold is met or exceeded, the all-or-none principle applies

The strength of stimulus is not coded by the amplitude of the AP, but by the frequency.

- When a greater stimulus strength is applied to a neuron identical AP’s are produced more frequently.

Overshoot

Hyperpolarization

All AP’s are of the same duration (~ 2 mSec) and amplitude (~ -70 to +30 mV)

Action potential – The role of ion channels

Refractory period

• As stimulus intensity increases, the frequency of AP’s increase

Time between successive AP’s is reduced

Another AP can not be produced until the preceding one has finished

Refractory period: Time during which the patch of axon membrane is unable to produce another AP

Value of the refractory period?

- Allows propagation of action potential

Effect of myelination

 Action potential is faster in myelinated fibers

The Velocity of an Action Potential

Effect of neuron diameter

 Larger diameter neurons conduct nerve impulses faster

 Larger diameter neurons present less resistance to current flow

Conduction of action potentials in unmyelinated axons - Contiguous conduction

Conduction speed: Nerve impulse travels 1 meter in 0.1s (100ms)

= 10 meters/second

Neurons have cable properties

• This means that neurons can transmit charges through its cytoplasm ~ 1-2mm

• However these cable properties are poor – Why ?

1. There is high internal resistance to the spread of charges 2. Many charges leak out of the axon membrane

Myelinated axon

• Myelin sheath acts as insulation

– Prevents flux of ions across the membrane

• Nodes of Ranvier: Interruptions in the myelin sheath (~1mm apart)

• Ion channels are concentrated at the nodes of Ranvier – This is where the AP’s occur

• Cable properties mean the AP’s jump from node to node – Saltatory conduction

– Conduction is faster in myelinated than unmyelinated axons

Conduction of action potentials in myelinated axons

- Saltatory conduction

Conduction speed: Nerve impulse travels 1 meter in 0.007s (7ms)

= 143 meters/second (14 times faster than in unmyelinated axon)

Nerve cell

Myelin sheath

Muscle

Degradation of myelin sheath in multiple sclerosis

Multiple sclerosis is an autoimmune demyleinating disease of the CNS

MRI scan showing lesions in MS brain

T-cells, macrophages & B-cells infiltrate the CNS and attack the myelin sheeth

resulting in demyelination

Dysregulated conduction in a demyelinated nerve fibres in multiple sclerosis

Normal

Multiple Sclerosis

Consequence of demyelination in MS

- Loss of axonal conduction for neurons of the CNS and in clinical disability

Symptoms of MS:

- Blurred vision - Muscle weakness - Ataxia

 Synapse: Site of functional connection between a neuron and another cell

CNS: Another neuron

PNS: Another neuron or an effector cell in a muscle or gland

The Synapse

Synapses

 Point of communication between neurones

 Most synapses involve neurotransmitters

 Synapses can be:

Excitatory

 Inhibitory

The two types of postsynaptic potentials are:

EPSP: Excitatory postsynaptic potentials IPSP: Inhibitory postsynaptic potentials

EAA

EAA

Ca++

+ + + + + +

Glutamate generates an excitatory post-synaptic potential (EPSP)

Glutamate (NMDA) receptor is a ligand-gated Ca²⁺ channel (Glutamate)

GABA generates an inhibitory post-synaptic potential

TIME MILLIVOLTS

THRESHOLD -60

-70

-80 -50

GABA

GABA

Cl-

- - - - - -

GABA_A receptor is a ligand-gated Cl^- channel

• EPSPs are graded potentials that can initiate an action potential in an axon

• EPSPs bring the RMP closer to threshold and therefore closer to an action potential

Excitatory Postsynaptic potentials (EPSPs)

• Neurotransmitter binding to a receptor at inhibitory synapses:

– Causes the membrane to become more permeable to potassium and chloride ions

• Leaves the charge on the inner surface more

negative (due to flow of K+ out of the cell and the flow of Cl^- in)

– IPSPs bring the RMP further away from the threshold

• Thereby reducing the postsynaptic neuron’s ability to produce an action potential

Inhibitory synapses and IPSPs

• A single EPSP cannot induce an action potential

• EPSPs must summate temporally or spatially to induce an action potential

• Temporal summation

– One pre-synaptic neuron transmits impulses in rapid- fire order

• Spatial summation

– Postsynaptic neuron is stimulated by a large number of pre-synaptic neurons at the same time

• IPSPs can also summate with EPSPs, canceling each other out

Summation

Recording electrode

Recording electrode

Integration of EPSPs and IPSPs occurs here

Key steps in chemical neurotransmission

1. Synthesis 2. Storage 3. Release

• Action potential

• Ca²⁺ influx

• NT release (Exocytosis)

4. Receptor binding & activation

– Generation of a postsynaptic potential

5. Inactivation

– Metabolism/Reuptake

Pre-synaptic neuron

Post-synaptic neuron

Ca²⁺

• AP arrives at the nerve terminal

• Nerve terminal membrane is depolarized

• Depolarization causes voltage regulated Ca²⁺ channels to open

• Ca²⁺ influx

What happens on the pre-synaptic side ?

Action potential

Ca²⁺

[Ca²⁺]i = 100 nM [Ca ²⁺]e = 1-2 mM (10,000 fold difference approx.)

⇨ Ca²⁺ enters the nerve terminal down the concentration gradient

Ca²⁺

• Ca²⁺ activates enzymes and proteins in the nerve terminal

• Synaptic vesicles fuse with the plasma membrane & release their contents into the synaptic cleft by exocytosis

What happens on the pre-synaptic side ?

Action potential

Ca²⁺

There is a time delay of 0.5ms in synaptic transmission

⇨ Time needed for Ca²⁺ to enter & cause exocytosis of transmitter

Generate EPSP

or IPSP Ca²⁺

Neurotransmitters

Action potential

Ca²⁺

Neurotransmitters can be either exicitatory or inhibitory

- Amount of neurotransmitter released is proportional to the frequency of action potentials produced at the nerve terminal

• Amines: Catecholamines, Acetylcholine, Serotonin

• Amino acids: Glutamate, GABA and Glycine

• Neuropeptides

 A neuron's RMP of –70 mV is maintained by the sodium- potassium pump.

 Changes in membrane potential occur when ion channels open, permitting ions to move from one side of the

membrane to the other.

 If the membrane potential depolarizes by 15 to 20 mV the threshold is reached, resulting in an action potential.

 Impulses travel faster in myelinated axons and in neurons with larger diameters.

 Saltatory conduction refers to an impulse traveling along a myelinated fiber by jumping from one node of Ranvier to the next.

 Action potential results neurotransmitter release

 The neurotransmitter can generate an IPSP or EPSP in the post-synaptic neuron

Summary: The Nerve Impulse