nervous system (BAI GIANG HE THAN KINH)

Role of Na+, K+ and ion channels in generating an action potential • Myelinated and unmyelinated nerve fibers •Transmission of nerve impulse in myelinated and unmyelinated axons • Syna

Physiology of the nervous system- Neurophysiology

Objectives:

Part 1: basic concepts in nerous system

•The Divisions of the nervous system Central nervous system (CNS), Peripheral nervous system (PNS), sensory (afferent) nervous system, motor (efferent) nervous system, somatic nervous system, autonomic nervous system: sympathetic and parasympathetic nervous system

• Neuron, the structural unit of the nervous system Types of neurons

• Glial cells and their function

•Resting membrane potential and action potential Role of Na+, K+ and ion channels in generating

an action potential

• Myelinated and unmyelinated nerve fibers

•Transmission of nerve impulse in myelinated and unmyelinated axons

• Synapse

• Synaptic transmission of nerve impulse

• Excitatory postsynaptic potential (EPSP) Inhibitory postsynaptic potential (IPSP)

•Spatial and temporal summation of postsynaptic potential

•Neurotransmitters

•Divergent and convergent pathway in the nervous system

Part2: major structures of the central nervous system and their main function

Part 3.The autonomic nervous system Structural organization of sympathetic and

parasympathetic systems and their function

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Specific terms and keywords

• Resting membrane potential

• Ion channels Voltage-gated ion channels

• Threshold

• Action potential/nerve signal/nerve impulse

• Action potential propagation/ transmission/conduction

• Synapse

• Synaptic transmission

Neurons and nervous systems in different phyla

• Nerve net (cnidarians: jellyfish,

anemones, hydra) neurons are

dispersed in a thin layer

• Centralized and cephalized nervous

system (flatworm, squid)

• Ganglionic central nervous system

(anthropods, annelids, molluscs)

• Columnar nervous system

complexity of organization of neurons into systems , rather than changes in neurons themselves

AHill, Wyse , Andersonn ingly Aimal physiology 2nd

e,2008

phân tán

Hạch

Hình ống

The divisions of the nervous system

• central nervous system- CNS

– Brain

– Spinal cord

• peripheral nervous system- PNS

– Nerve fibers: 12 pairs of cranial nerves , 31 pairs of spinal nerves

– Ganglion/ganglia

– 2 subdivions :

• Afferent /sensory division

• Efferent/motor division:

– somatic motor nervous system: skeletal muscles

– autonomic nervous system-ANS: smooth muscles, glands, heart muscle

» sympathetic nervous system

» parasympathetic nervous system

Fig.7.1 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Cellular components of the

nervous system

• Neuron

• Glial cells (70-90%)

• neural impulse transmission:

– Axon hillock – Axon terminal

• Mature neurons can not divide

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

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Structural classification of neurons

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Classification of neuron types

• one axon and one axon-like dendrite

• Sensory neuron in the eyes, roof of the nasal cavity, and inner ear

– multipolar neuron

• Many dendrites and one axon

• Interneuron and motor neuron

Neuroglia (glial cells)

• Rudolf Virchow (1821-1902) coined the term (1846)

• Functions:

– Structural/physical support to neurons

– Metabolic support to neurons

– Component of blood-brain barrier

– Protection of neurons from pathogens and removal of dead neurons – Production of cerebrospinal fluid

– Formation of myelin sheath surrounding axons

• Types of glial cells:

+ Astrocyte:CNS + Ependymal: CNS: cerebrospinal fluid + Microglia: macrophages differentiated in CNS, + Oligodendrocyte: CNS

+ Schwann cells: PNS

Tế bào thần kinh đệm

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Astrocyte and microglia

Astrocytes (star-shaped cells)

- metabolic support to neuron: provide lactate and glycogen

- component of the blood–brain barrier

- regulate the external chemical environment of neurons:

removal of excess ions (K+), recycling excess

Schwann cells

• Forming myelin sheath surrounding axons in the PNS

• One Schwann cell forms one myelin sheath surrounding a small portion of an axon

• Myelinated axons: myelin sheath and nodes of Ranvier

fig.cox.miami.edu/ /neuro/neurophysiology.htm

PNS

How do neurons function?

• Receive information (dendrites)

•Integrate information (cell body)

• Send information (axon):

+ down along the axon + out to other neurons

• information = electrical signal

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Electrical properties of living cells

-Negatively and positively charged ions

-Negatively and positively organic molecules -Ion channels

-Permeability of membrane for ions

Localization of ion channels in neurons

• Each region (in a neuron) has specific types of ion channels

• Most of the ion channels are gated (can open or close)

permeability of the plasma membrane for a specific ion

leading to a change in electrical properties of the cell or the release of neurotransmitters

• Leak channels (none gated channels): always open, found throughout a neuron -> resting membrane potential

• Ligand-gated channels: open or close in response to the

binding of a chemical messenger to a specific receptor in the plasma membrane

• Voltage-gated channels: open or close in response to

changes in membrane potential:

– voltage-gated Na+ and K+ channels mostly found in axon and axon hillock

– Ca2+ channels in axon terminals

Resting membrane potential of a neuron

• A cell at rest has a potential difference across its membrane: inside of the

cell is negative charge (relative to the outside): resting membrane potential (resting Vm)

• For a neuron Vm= -70mV

• Membrane potential is defined as the potential inside the cell relative to outside

• Neuron communicate by generating electrical signals in the form of

changes in membrane potential Some of these changes in membrane

potential trigger the release of neurotransmitters which then carries signal

to another cells

– What causes the resting membrane potential ?

– What causes the membrane potential to change ?

What causes the resting membrane potential?

• Concentration gradients (created by Na+/K+ pump ) of ions

(sodium and potassium ions) across the plasma membrane

• The presence of ion channels (leaking channels) in the

plasma membrane (mainly K+ channels when cells are at

rest)

• The differences in the permeability of the plasma membrane

to these 2 ions

• Chemical and electrical forces for moving sodium and

potassium ions across the plasma membrane

Na+

Cl-15.04.0

145.0115.0

Establishing a steady-state resting membrane potential

Fig.7.8 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Nernst Equation :

to calculate the equilibrium potential across a cell’s membrane for one ion given its concentrations inside and

outside the cell are known

• Ei: equilibrium potential for ion I

• Z: the valence of the ion

• (I)o: Concentration of I ion outside the cell

• (I)i: concentration of I ion inside the cell

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Goldman-Hodgkin-Katz (GHK) Equation

To calculate membrane potential in case only K+ and Na+ are permeant and their concentration inside and outside the cell are known

Gated-ion channels open or close in response to a stimuli -> change the membrane permeability for ions

-> change in membrane potential

Electrical signal: changes in membrane

potential

Change in membrane potential is defined based on the direction of change relative to the resting membrane potential

• hyperpolarization

a change to more negative value:

• Depolarization: a change to less negative/positive value

• Repolarization:

potential returns

to the resting membrane potential following

a depolarization

AHill, Wyse , Andersonn Aimal physiology 2nd e,2008

Neurons communicate via 2 types of

electrical signals

• Graded potentials

• Action potentials

Graded potentials

• Graded potentials are small changes

in the membrane potential (Vm)

in response to a stimulus

Fig.7.12 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Graded potential is decremental

• A graded potential dissipates

as it moves

to adjacent areas of the plasma

membrane

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Graded potentials can sum temporally and spatially The sum may reach the threshold for triggering an action potential

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

thoi gian khong gian

Action potentials (AP) result from changes in

membrane permeabilities to ions

AP results from three overlapping permeability changes:

1 increased permeability

to Na+ by the rapid opening of voltage-gated Na+ channels

2 Decreased permeability

to Na+ by inactivation of Na+ channels

3 Increased permeability to K+ by the the slower opening of voltage-gated K+ channels

AHill, Wyse , Andersonn Aimal physiology 2nd e,2008

Action potentials result from changes in membrane

• Depolarization (membrane potential changes from -70

to +30mV: due to sudden and dramatic increase in permeability to sodium-> increase Na+ movement into the cell

• Repolarization: membrane potential returns (from +30mV) back to -70mV: Na+ permeability decrease, K+ permeability increases: K+ move out of the cell

• After-hyperpolarization: permeability of K+ remains high for a brief time (5-15 msec) after the membrane

potential reaches the resting membrane potential

• Initiation of APs follows the all-or-none principle: whether a membrane is depolarized to threshold or above, the amplitude of the resulting action potential is the same; if the membrane is not depolarized to

threshold, no action potential occurs

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Fig.7.14

Fig.7.17

• During relative refractory period, a second AP can be generated but

only when the second stimulus is stronger than needed to get

threshold potential in resting conditions

Fig 7.18 C.L Standfield.2011.

Principles of Human Physiology, 4 th edition.

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Action potential propagation in unmyelinated axon

• Continuous conduction

Fig 7.20 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Lan truyeàn

Action potential propagation in

Classification of nerve fibers

• Based on conduction velocities of nerve signal of the nerves

• These conduction velocities depend on diameter of the nerves and the presence of myelin in the nerves

• Myelinated nerves with largest diameter have highest

conduction velocities

• Neurotoxins are toxins interfering with normal function of the nervous system

• Some affecting ion channels

• Tetrodotoxin (TTX) from blowfish/puffer fish, saxitoxin (STX) from some marine

dinoflagellate and a

freshwater cyanobacterium,

toxic at nanomolar concentrations

– TTX blocks voltage-gated Na+ channels

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Signal transmission between neurons:

synaptic transmission

Synapse

• A specialized site

of communication btw 2 neurons, btw a neuron and

an effector, or btw a nonneural sensory cell and

a neuron

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Types of synapses

• Electrical synapses : gap junction made

by protein channels bridging the gap

between two cells

– Transmit signals instantaneously

• Chemical synapses

– Ionotropic chemical synapses

– Metabotropic chemical synapses

Structure of a chemical synapse

Fig.8.2 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Chemical synaptic transmission

1 Stimulus = action potential

2 action potential -> Ca2+

channels open, Ca2+ move into presynaptic knob

3 Ca 2+ enters the cell and

triggers the release of neurotransmitter by exocytosis

4 Neurotransmitter diffuses

across the synaptic cleft,

binding to receptors on the postsynaptic membrane

Ionotropic chemical synapses release neurotransmitters

binding to ionotropic receptors (channel-link receptors)

• The receptor is also an ion channel (ligand- gated ion channel)

• Neurotransmitter binds to receptor -> ion channel opens-> ion movement through postsynaptic membrane

-> postsynaptic potential (PSP)

• Fast response (few msec)

Fig.8.3.C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Metabotropic chemical synapses release neurotransmitters binding to metabotropic receptor ( G-protein linked receptor)

• G-protein-regulated ion channels respond to the binding of

neurotransmitter slowly (msec-hours)

• Slow response

(Cellular metabolism, gene expression) Fig.8.3 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Excitatory and Inhibitory neurons

• Neuron releases neurotransmitters causing

depolarization of postsynaptic membrane

(Na+ move into the cell) ->

EPSP- excitatory postsynaptic potential) ->

Excitatory neuron->

excitatory synapse

• Neuron releases neurotransmitters causing

hyperpolarization) of postsynaptic membrane (K+move in or Cl- move out of the cell)- IPSP- inhibitory postsynaptic potential

->Inhibitory neuron-> inhibitory synapse

One neurotransmitter may mediate different postsynaptic

actions through different postsynaptic receptors

• Acetycholine

– binds ligand-gated channels / ionotropic

– binds G-protein coupled receptor/

heart muscles

Neural integration: One neuron may contact many

other neurons through its collaterals - divergent pathway

Fig 8.7 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Neural integration: one neuron can receive information

from many other neurons - Convergent pathway

Fig.8.7 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Spatial and temporal summation of

postsynaptic potentials

• EPSPs and IPSPs

are graded potentials, thus they can summate temporally and

spatially

• Axon hillock acts

as an integrator for the summation

Fig.8.8 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Neurotransmitters (NTs)

•Most synapses in the CNS use amino acid neurotransmitters Most fast

•Biogenic amines are found in few neurons but these neurons have widely

projecting endings Many receptors for these NTs have slow actions that

modulate neuronal activities, rather than mediating fast excitation or inhibition

•Peptides are present in substantial minorities of CNS neurons A

neuroactive peptide may be co-released with one or more small molecule

neurotransmitters and may function as a cotransmitter with slow synaptic effects

C.L Standfield.2011 Principles of Human Physiology, 4 th edition.

Neurotransmitters (NTs) and drug’s target

• chemical receptor binding: potential target for a drug:

messenger/neurotransmitter Morphine as pain killer

- Glutamate: excitatory neuron

- Serotonin and depression

- Benzodiazepines (as Valium), sleeping aids (zolpidem), Alcohol and anxiety (enhance action of GABA)

Fig.8.2 C.L Standfield.2011 Principles of Human Physiology, 4 th edition.