Introduction, resting and action potential · Introduction, resting and action potential Boris...
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Neurophysiology I
Introduction, resting and action potential
Boris Mravec 2020
(Mader, 2001)
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
Transmission of signals in the bodyCommunication between cells
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
Transmission of signals in the bodyCommunication between cells
• 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
(Freudenrich and Tortora, 2011)
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
(Freudenrich and Tortora, 2011)
Cerebrospinal fluid
Cerebrospinal fluidFunctions
• protection
• transport of chemicals
(Siegel and Sapru, 2014)
Cerebrospinal fluidComposition
(Siegel and Sapru, 2014)
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
(Siegel and Sapru, 2014)
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
(Siegel and Sapru, 2014)
NeuronsMorphology
(Martini et al., 2014)
NeuronsAxonal transport
(Siegel and Sapru, 2014)
NeuronsClassification according to morphology
(Siegel and Sapru, 2014)
NeuronsClassification according to morphology
(Martini et al., 2014)
Glia cells
Glia cellsClassification
(Martini et al., 2014)
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
(Siegel and Sapru, 2014)
Glia cellsIn CNS
Glia cellsIn CNS
(Martini et al., 2014)
Glia cellsIn CNS and PNS
(Siegel and Sapru, 2014)
CNS
PNS
Glia cellsIn PNS
(Martini et al., 2014)
Glia cellsRole in neuronal injury
(Siegel and Sapru, 2014)
Glia cellsOther cells in the nervous system
(Siegel and Sapru, 2014)
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
Resting membrane potentialTransmembrane potential
• 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
Resting membrane potentialTransmembrane potential
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
Resting membrane potentialTransmembrane potential
(Martini et al., 2014)
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
(Martini et al., 2014)
(Bear et al., 2015)
Resting membrane potentialPotasium ion gradients
Resting membrane potentialSodium ion gradients
(Martini et al., 2014)
Resting membrane potentialTransmembrane potential
• 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
(Siegel and Sapru, 2014)
Alterations of the membrane potential
Graded potentials
(Silverthorn, 2012)
Graded potentialsMechanisms
Graded potentialsIon channels role
(Martini et al., 2014)
(Martini et al., 2014)
Graded potentialsMechanisms
(Silverthorn, 2012)
Graded potentialsMechanisms
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
(Martini et al., 2014)
Graded potentialsDepolarization and hyperpolarization
Alterations of the membrane potential
Action potential
Action potentialBasics
(Martini et al., 2014)
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)
Action potentialMechanisms
(Martini et al., 2014)
Action potentialMechanisms
(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
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
(Martini et al., 2014)
Propagation of action potential
Propagation of action potentialAll-or-None Law
(Martini et al., 2014)
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
(Martini et al., 2014)
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
(Martini et al., 2014)
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
(Martini et al., 2014)
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
(Siegel and Sapru, 2014)
Propagation of action potentialDiameter of fibers and conduction velocity
References
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