Introduction, resting and action potential · Introduction, resting and action potential Boris...

Neurophysiology I

Introduction, resting and action potential

Boris Mravec 2020

(Mader, 2001)

http://www.google.sk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj4--bVpJrLAhWoDpoKHXUQDDQQjRwIBw&url=http%3A%2F%2Fbizlifes.net%2Fdiscovery%2F886-compare-number-of-cells-in-human-body-and-galaxies-in-the-universe.html&bvm=bv.115339255,d.bGs&psig=AFQjCNGgCaVrvPXgO49e2OHJhXM-l28imw&ust=1456742937855302

Transmission of signals in the bodyCommunication between cells

• Intermediary metabolism

• Response to external signals

• Cell growth

• Cell division activity

• Differentiation and development: coordination of expression programs

• Cell motility

• Cell morphology


Intercellular signaling:

• communication between cells

Intracellular signaling:

• signaling chains within the cell, responding to extracellular and

intracellular stimuli

(Krauss, 2014)

Autocrine signaling: secreted molecules diffuse

locally and trigger a response in the cells that secrete

them.

Paracrine signaling: secreted molecules diffuse

locally and trigger a response in neighboring cells.

Endocrine signaling: secreted molecules diffuse into

the bloodstream and trigger responses in target cells

anywhere in the body.

Synaptic signaling: neurotransmitters diffuse across

synapses and trigger responses in cells of target

tissues (neurons, muscles,

or glands).

Neuroendocrine signaling: neurohormones diffuse

into the bloodstream and trigger responses in target

cells anywhere in the body.

(Reece et al., 2010)

Intercellular communication by secreted molecules


• Nervous system enables rapid and targeted communication

• Endocrine system enables slower and more diffuse

communication

• Nervous and endocrine control systems overlap

• Transmission of signals from external environment

• Transmission of signals from internal millieu

(Rhoades and Bell, 2012)

Intercellular communication – the need for neurons

(Carpenter and Reddi, 2012)

Intercellular communication – the need for neuronsDiffusion time

(Carpenter and Reddi, 2012)

Intercellular communication – the need for neuronsSpecificity

(Silverthorn, 2012)

Intercellular communication – the need for neuronsComplexity

Nervous system interacts

with endocrine and immune system

(Ashley and Demas, 2017)

Neuro-endocrine-immune interactionsBasis for complex regulations

(Procaccini et al., 2014)

Neuro-endocrine-immune interactionsBasis for complex regulations

Nervous system

Principal regulatory system of human organism

Nervous system is principal regulator participating on preservation of internal

environment stability (homeostasis) in spite of changes in external and internal

environment

Integration: central nervous system

Encephalization – encephalon (the brain): the amount of brain mass related to an animal's

total body mass. Quantifying an animal's encephalization has been argued to be directly

proportional, although not equal, to that animal's level of intelligence

Corticalization – cortex: the youngest and the most complex structure in the known world

=Centralization of regulatory functions into the brain cortex

Functional hierarchy – youngest structures regulate body functions through

modulation of activity of older structures

(Bear et al., 2015)

Some major disorders of the nervous system

Disorder Description

Alzheimer’s disease A progressive degenerative disease of the brain, characterized by dementia and always fatal

Autism A disorder emerging in early childhood characterized by impairments in communication and social

interactions, and restricted and repetitive behaviors

Cerebral palsy A motor disorder caused by damage to the cerebrum before, during, or soon after birth

Depression A serious disorder of mood, characterized by insomnia, loss of appetite, and feelings of dejection

Epilepsy A condition characterized by periodic disturbances of brain electrical activity that can lead to

seizures, loss of consciousness, and sensory disturbances

Multiple sclerosis A progressive disease that affects nerve conduction, characterized by episodes of weakness, lack

of coordination, and speech disturbance

Parkinson’s disease A progressive disease of the brain that leads to difficulty in initiating voluntary movement

Schizophrenia A severe psychotic illness characterized by delusions, hallucinations, and bizarre behavior

Spinal paralysis A loss of feeling and movement caused by traumatic damage to the spinal cord

Stroke A loss of brain function caused by disruption of the blood supply, usually leading to permanent

sensory, motor, or cognitive deficit

• General neurophysiology – how the brain works, how the brain communicates with other parts of the body, neurons and glia

• Transmembrane potential

• Graded potential

• Action potential and its transmission via nerves

• Synaptic transmission of signalls, neurotrransmitters and neuromodulators

• Autonomic nervous system

• Excitation and mechanics of skeletal muscle contraction

• Excitation and mechanisms of smooth muscle contraction

General neurophysiologyOutline of the lectures

Central and peripheral nervous system

Nervous systemDivisions

(Martini et al., 2014)

(Bear et al., 2015)

Central and peripheral nervous systemThe brain

(Bear et al., 2015)

Central and peripheral nervous systemSpinal cord and peripheral nerves

Nerve fibers - axons – connections to effectors (muscles and glands)

• motor nerve fibers

• autonomic (vegetative) nerve fibers

- sympathetic

- parasympathetic

• sensory nerve fibers

REFLEXES

SPINAL CORD - reflexes,

BRAIN STEM - breathing, blood pressure

Very quick stereotypic reactions

“brain of the snake” (visceral)

EMOTIONS

PALEOCORTEX

SUBCORTICAL NUCLEI - life and species preservation, survival

“brain of the horse” (emotional)

COGNITION

Neokortex – the highest level of brain functions – learning and memory

Cognition – homo sapiens

“brain of a man” (cognitive)

Functional division of the nervous systemBasics facts

Functional division of the nervous systemBasics facts

Sensory function (information input)

Neurons in the peripheral nervous system (PNS) monitor changes in internal and external

environments, such as changes in blood pressure, injuries, touch, and pain, and send this

information to the central nervous system (CNS).

Integrative function (information processing)

Neurons in the CNS analyze sensory information and make decisions unconsciously or

consciously. Conscious decisions require perception (or mental awareness) and higher level

processing.

Motor function (information output)

After processing information and making decisions, CNS neurons send commands to muscular

or glandular effectors that carry out responses such as muscle contraction/relaxation or

increased/decreased secretion of substances such as oil or sweat.

(Freudenrich and Tortora, 2011)

Functional division of the nervous systemSensory systems

The afferent (sensory) nervous system consists of a variety of nerve

receptors and their associated nerve fibers:

• Somatosensory receptors are associated with the muscles, joints, and skin

• Special sense receptors are found in the ear, eye, nose, and tongue

• Autonomic sensory receptors are found in the internal organs


Functional division of the nervous systemMotor systems

The efferent (motor) nervous system is composed of motor nerve fibers that

regulate the activities of muscle and glandular tissues throughout the body.

This system can be subdivided into three sections:

• The somatic nervous system (SoNS) deals with initiating voluntary (under

conscious control) skeletal muscle actions that move the body around in

space.

• The autonomic nervous system (ANS) regulates involuntary functions

(such as heart rate, breathing rate, and body temperature) involving cardiac

muscle, smooth muscle, and glandular tissue. This system consists of two

divisions, sympathetic and parasympathetic, which have opposite effects.

• The enteric nervous system (ENS) is an intricate network of nerve fibers

within the digestive organs that regulates the involuntary functions of the

digestive system and interacts with the ANS.

• The neuroendocrine system


Cerebrospinal fluid

Cerebrospinal fluidFunctions

• protection

• transport of chemicals

(Siegel and Sapru, 2014)

Cerebrospinal fluidComposition


Constituent Serum Cerebrospinal

fluid

Protein (g/L) 60 - 78 0.15 - 0.45

Glucose (mmol/L) 3.9 - 5.8 2.2 - 3.9

Ca2+ (mmol/L) 2.1 - 2.5 1 - 1.35

K+ (mmol/L) 4 - 5 2.8 - 3.2

Na+ (mmol/L) 136 - 146 147 - 151

Cl- (mmol/L) 98 - 106 118 - 132

Mg2+ (mmol/L) 0.65 - 1.05 0.78 - 1.26

Blood-brain barrier

Blood-brain barrierComposition

(Felten and Shetty, 2009)

Blood-brain barrierCircumventricular organs

• secretory

• sensory


Cellular composition of the nervous system

Cellular composition of the nervous system

• neurons

• glia cells

Neurons

NeuronsNeuron doctrine

• the nervous system is made up of discrete individual cells, a discovery made by

Santiago Ramón y Cajal (neuron doctrine)

• neuron – basic morphological and functional unit of the nervous system

• neurons:

- receive, process and transmit signals

- induce responses

NeuronsMorphology


NeuronsAxonal transport


NeuronsClassification according to morphology


Glia cells

Glia cellsClassification


They serve as the functional support

for neurons

Neuroglia – term originated from

„glue“ (introduced by Rudolf

Virchow in 1854)

Astrocytes

• Involved in neuronal nutrition

• Influence the EC environment

• Influence the synaptic transmission

by neurotransmitter reuptake

Oligodendrocytes

• Myelination of axons

• Influence the transmission speed

Microglia

• Immune cells in the brain

• Have the capability of phagocytosis


Glia cellsIn CNS

Glia cellsIn CNS


Glia cellsIn CNS and PNS


CNS

PNS

Glia cellsIn PNS


Glia cellsRole in neuronal injury


Glia cellsOther cells in the nervous system


Resting membrane potential

Resting membrane potentialTransmembrane potential

(Bear et al., 2015)

Relative concentrations of relevant ions inside and outside the neuron and the forces acting on

them


• Transmembrane potential dependes on the permeability of the membrane for every

important ion and the balanced potential for every diffusible ion

• All cells have the membrane potential, but not all have the same value

• Most of the cells have transmembrane potential in the range of –65 mV to –90 mV

• Only nerve and muscle cells could change the potential and elicit action potential

Na/K pumps remain the equilibrium


Ions diffuse down their electrochemical gradient, usually through pores called ion channels.

Ion channels can be highly selective for the chemical species they let through. Sodium's

diffusion across the membrane is facilitated by an ion channel. It is selective for Na+ by

the size of the pore in the channel and the charges on amino acids inside the pore. K+

is too big to pass through; Cl− is too negative.

Resting membrane potentialIon channels role



Explorative electrode is

insetred inside the cell,

therefore the value is negative

(the inside is negative in

comparison with the outside)

Resting membrane potentialPotasium ion gradients


(Bear et al., 2015)

Resting membrane potentialPotasium ion gradients

Resting membrane potentialSodium ion gradients



• Because the plasma membrane is highly permeable to potassium ions, the resting

membrane potential of approximately –70 mV is fairly close to –90 mV, the equilibrium

potential for K+.

• The electrochemical gradient for sodium ions is very large, but the membrane’s permeability

to these ions is very low. Consequently, Na+ has only a small effect on the normal resting

membrane potential, making it just slightly less negative than the equilibrium potential for K+.

• The sodium–potassium exchange pump ejects 3 Na+ ions for every 2 K+ ions that it brings

into the cell. It serves to stabilize the resting membrane potential when the ratio of Na+ entry

to K+ loss through passive channels is 3:2.

• At the normal resting membrane potential, these passive and active mechanisms are in

balance. The resting membrane potential varies widely with the type of cell. A typical neuron

has a resting membrane potential of approximately –70 mV.

Resting membrane potentialNernst and Goldman Equations


Alterations of the membrane potential

Graded potentials

(Silverthorn, 2012)

Graded potentialsMechanisms

Graded potentialsIon channels role


(Silverthorn, 2012)


EPSP is caused by opening of Na

channels in the postsynaptic membrane

EPSP is caused by the opening of Cl

channels in the postsynaptic membrane

Graded potentialsExcitatory and inhibitory potential


Graded potentialsDepolarization and hyperpolarization

Alterations of the membrane potential

Action potential

Action potentialBasics


Neurons communicate via electrical and chemical signals

Action potentialBasics

Only a few types of cells can alter their membrane potential by varying the

membrane permeability to specific ions in response to stimulation

Ability to change the membrane potential have nervous and muscle cells

thanks to IRRITABILITY OR EXCITABILITY of their membranes. The threshold

stimulus brings about the action potential which is conducted by an axon

membrane

CONDUCTIVITY – the membrane is excited by the stimulus and when the axon

membrane is depolarized to a threshold level the Na gates open and the

membrane becomes permeable to Na (transpolarization) valid for the axon

ACTION POTENTIAL conduction

1) all or none law

2) refractory periods

3) intensity is coded by frequency

Action potentialMechanisms

Stimulation of the membrane by subthreshold stimulus elicits local graded excitation with

decreasing of potential difference on the membrane (depolarization) or with decreasing

potential difference (hyperpolarization)

Stimulation with threshold stimulus initiates nerve impulse – action potential (on axon

hillock) and its conduction via the axon spikes – transpolarization

AP is caused by opening of Na channels after the threshold stimulus

(Silverthorn, 2012)


(Fox, 2015)

Temporal summation: repeated stimuli within a relatively short period of time can have a

cumulative effect

Spatial summation: stimuli occurring at different locations can have a cumulative effect.

Sir John Eccles (1903-1997)

showed temporal summation

in single cells. Won the Nobel

Prize in 1963 for his work on

how inhibitory and excitatory

processes occur at the

synapse.

Action potentialTemporal vs. spatial summation

http://nobelprize.org/medicine/laureates/1963/eccles-bio.html

Action potential is produced by an

increase in sodium diffusion followed

by an increase of potassium diffusion

Both depolarization and repolarization

are produced by the diffusion of ions

down their concentration gradients

The Na/K pumps then rebuild the

concentration gradients of both ions

(sodium and potassium)

treshold

Once a region of the axon membrane has been

depolarized to a threshold, the duration and the

amplitude of the AP is independent of the strenght

of the stimulus – ALL OR NONE LAW

Action potentialNerve impulse

Action potentialNerve impulse

Action potentialNa/K ATPase

Action potentialRefractory periods


Propagation of action potential

Propagation of action potentialAll-or-None Law


Constant regeneration of depolarization of the membrane conduction of action potentials

without decrement

osciloscop

Propagation of action potentialConduction of the nerve impulse

Propagation of action potentialContinuous propagation along an unmyelinated axon


Conduction on unmyelinated fibers

= without myelin sheath around the axon

Action potential is regenerated on the

adjacent region of the excitable

membrane of an axon

Each AP injects positive charges (sodium

ions) into the axon. These are conducted

by the cable properties of the axon to an

adjacent region that still has a membrane

potential of –65 mV. When this adjacent

region of the membrane reaches

threshold level of depolarization

It too produces an AP as its voltage

regulated gates open

Propagation of action potentialSaltatory propagation along a myelinated axon


Conduction on myelinated fibers =

with myelin sheath wrapped around

the axon made of Schwann cells

Action potential is propagated by

SALTATORY CONDUCTION

(“jumps” from one Ranvier node to

another)

Propagation of action potentialA Comparison of Graded Potentials and Action Potentials


Graded Potentials Action Potentials

Depolarizing or hyperpolarizing Always depolarizing

No threshold value Depolarization to threshold must occur before

action potential begins

Amount of depolarization or hyperpolarization

depends on intensity of stimulus

All-or-none; all stimuli that exceed threshold

produce identical action potentials

Passive spread from site of stimulation Action potential at one site depolarizes adjacent

sites to threshold

Effect on membrane potential decreases with

distance from stimulation site

Propagated along entire membrane surface

without decrease in strength

No refractory period Refractory period occurs

Occur in most plasma membranes Occur only in excitable membranes of specialized

cells such as neurons and muscle cells


Propagation of action potentialDiameter of fibers and conduction velocity

References

• Ashley NT, Demas GE. Neuroendocrine-immune circuits, phenotypes, and interactions. Horm Behav

2017; 87: 25-34.

• Bear MF, Connors BW, Paradiso MA. Neuroscience: exploring the brain. Baltimore: Lippincott Williams &

Wilkins, 2015, 975 pp.

• Carpenter R, Reddi B. Neurophysiology: A Conceptual Approach: CRC Press, 2012, 448 pp.

• Felten DL, Shetty A. Netter's Atlas of Neuroscience: Saunders, 2009, 464 pp.

• Fox S. Human Physiology: McGraw-Hill Education, 2015, 832 pp.

• Freudenrich C, Tortora GJ. Visualizing Anatomy and Physiology: Wiley, 2011, 608 pp.

• Krauss G. Biochemistry of Signal Transduction and Regulation. Weinheim: Wiley-VCH, 2014, 844 pp.

• Mader SS. Human Biology (Student Study Guide): McGraw-Hill College, 2001; 514 pp.

• Martini FH, Nath JL, Bartholomew EF. Fundamentals of Anatomy & Physiology: Pearson, 2014, 1264 pp.

• Procaccini C, Pucino V, De Rosa V, Marone G, Matarese G. Neuro-endocrine networks controlling

immune system in health and disease. Front Immunol 2014; 5: 143.

• Reece JB, Urry LA, Cain ML, Wasserman SA, Minorsky PV, Jackson RB. Campbell Biology: Benjamin

Cummings, 2010; 1464 pp.

• Rhoades RA, Bell DR. Medical Physiology: Principles for Clinical Medicine: LWW, 2012; 851 pp.

• Siegel A, Sapru HN. Essential Neuroscience: Lippincott Williams and Wilkins, 2014; 608 pp.

• Silverthorn DU. Human Physiology: An Integrated Approach: Pearson, 2012, 992 pp.

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