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Description : Check out this medical presentation on Neurology, which is titled "BIOPHYSICS OF ACTION POTENTIAL & SYNAPSE", to know about the biophysics of action potential and synapse.

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Published on : Aug 23, 2021 | Views : 2644 | Downloads : 6

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BIOPHYSICS OF ACTION POTENTIAL & SYNAPSE Ivan Poliaček
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Excitable tissues - neuron (nerve tissue) - muscle fiber (muscle tissue) Neuron - primary structural and functional unit of nerve tissue (brain, spinal cord, nerves, sensory cells) - 4 – 130 μm soma dendrite nucleus axon terminal myelin sheath axon hillock initial segment node of Ranvier Schwann cell
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Propagation of neuronal excitation from dendrites to the axon dendrites soma axon with an axon collateral
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Membrane potential, membrane depolarization, hyperpolarization
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Cell membrane - reminder double-layer of phospholipide + cholesterol + proteins
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INTRA & EXTRA-CELLULAR ION CONCENTRATIONS ion inside outside (e.g. plasma) Na+ 12 mM 145 mM K+ 140 mM 4 mM Cl- 4 mM 115 mM HCO3 - 12 mM 30 mM protein - 140 mM 10 mM Ca++ 0,0001 mM 2 mM
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A magnitude is determined by concentrations & permeabilities of membrane for potasium, chlorine and sodium P K+ , P Na+ , P Cl- - permeabilities for K+, Na+, Cl- [K+], [Na+], [Cl-] - concentrations Membrane potential - Goldman equation What does keep these concentrations uneven? Is interior of the cell negatively charged? How can be membrane potential altered? What is responsible for permeability changes? How will changes in K+, Na+, Cl- permeabilities change membrane potential? What is term for lower MP – more polarized cell membrane? What is the term for higher MP – less polarized cell membrane? Resting membrane potential for neuron - about -70 mV 100 : 4 : 45
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Depolarization – less polarization = reduced magnitude of membrane potential (e.g. from -70 mV to -60 mV or more) Hyperpolarization – - more polarization = increased magnitude of membrane potential (e.g. from -70 mV to -80 mV) Graded (local) responses = graded depolarizations or hyperpolarizations : - electricity - chemicals - generator potential (sensory) - synaptic EPSP (depolarization) IPSP (hyperpolarization)
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Neuronal recording Rest # 1
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SYNAPSE neurons signal to each other or to muscles or glands Electrical synapses – electric signal goes through „gap junction“ (bidirectional) Chemical synapses – chemical transmission (one-way) one-directional from a presynaptic to a postsynaptic cell 1 mm3 of human cerebral cortex - about a billion of synapses
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Axo-dendritic synapses Synapses: - axo-dendritic - axo-somatic - axo-axonal
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neuron
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Action potential comes via axon to the terminal at pre-synaptic membrane depolarization opens voltage gated Ca channels - Ca++ diffuse into neuron Ca++ inside - vesicles towards the membrane (proteins stenine and neurine) - exocytosis – release of neurotransmitter (mediator) in the synaptic cleft Synaptic transmission
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3. diffusion of mediator molecules through the cleft (30-50 nm) mediator molecules activates receptors on subsynaptic part of postsynaptic membrane Synaptic transmission IONOTROPIC receptors – ligand-gated channels producing EPSP or IPSP at post-synaptic cell METABOTROPIC receptors – mediator at extracellular domain activates intracellular G-proteine leading to the intracellular signaling (gene expression, chemical reactions, channels opening / closing – membrane permeability changes)
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Summary: - action potential - voltage gated Ca channels - Ca++ influx - vesicles exocytosis - neurotransmitter (mediator) release - its diffusion through the cleft - interaction with receptors (e.g. ligand gated channels) How does action stop? elimination of neurotransmitter - reabsorbed by the presynaptic cell (re-packaged into vesicles) - broken down metabolically - diffused away
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Neurotransmitters chemically : aminoacids (glutamate, GABA, aspartate, glycine), peptides (vasopresin, somatostatine, neurotensine,...), monoamines (norepinephrine, serotonine, acetylcholine,...) Excitatory : - acetylcholine (neuromuscular junction) - glutamate Inhibitory : - GABA - glycine (spinal reflexes) excitation – inhibition mostly determined by receptor In the brain are essential: glutamate and GABA
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Rest # 2 Comments and requests are welcomed. Why are chemical synapses called chemical? What ion initiates synaptic transmission? Where is neuromediator stored? Where is it released? Where does neurotransmitter act? What is main difference between metabotropic receptor and ligand gated channel? What is the difference between ligand gated and voltage gated channel? Where are amployed ligand and where voltage gated channels in the synaptic transmission?
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Summation of postsynaptic potentials (stimulation of several synapses with ligand gated ion channels)
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EPSP – excitatory post-synaptic potential that depolarize IPSP – inhibitory post-synaptic potential that hyperpolarize Higher magnitude of PSP ? more neurotransmitter (and more receptors), the membrane already partially depolarized, for how long is neurotransmitter available (it must be quickly removed from the cleft or inactivated) Further from synapse (subsynaptic membrane) e.g. at axon hillock - less effect of PSP – it is GRADED and LOCAL electrical response that spreads with FALLOFF
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SUMMATION of PSPs 1 EPSP - rare to the threshold , but temporal summation of 2 EPSP additive effect of many synaptic potentials at a neuron if : - the time span between the stimuli is short - temporal summation - they arrive at a given region of a neuron - spatial summation
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SUMMATION of PSPs 1 EPSP - rare to the threshold , but spatial summation of 2 EPSP additive effect of many synaptic potentials at a neuron if : - the time span between the stimuli is short - temporal summation - stimuli arrive at several synapses of neuron - spatial summation
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Synaptic integration - The combining of EPSPs and IPSPs on a neuron. - In order for an action potential = ACTIVATION to occur, the threshold depolarization has to be reached at initial segment = axon hillock = trigger zone
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action potential arises at trigger zone = initial segment if the depolarization there reaches the threshold dendrites soma axon with an axon collateral
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I recommend to search GOOGLE summation of postsynaptic potentials at the axon hillock Animation 5.2 - Summation of Postsynaptic Potentials and see the following http://sites.sinauer.com/neuroscience5e/animations05.02.html Suggestions what is important and how to remember that important are appreciated, aren’t they? Rest # 3
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ACTION POTENTIAL Action potential (nerve impulse) - at excitable conductive tissues = nerve fibers & muscle cells if depolarization reaches the gate threshold = firing level. It is all-or-none (it happens or do not happen). stimulation rising phase depolarization falling phase repolarization hyperpolarization
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- Local (graded) depolarization to the threshold - firing level - Na channels open (voltage gated) - Na+ influx - rapid depolarization - SPIKE - even transpolarization – positive charge at internal side of membrane for a short moment (and negative outside) - Na channels close (voltage gated) and K channels open (voltage gated) – Na+ influx STOP + K+ efflux - rapid repolarization 500 times Na permeability At rest permeabilites for K+ : Na+ : Cl- 100 : 4 : 45 At spike depolarization 100 : 2000 : 45
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threshold and rising phase – Na channels are opening the peak – Na+ permeability maximal, Na channels slowly shut off – transpolarization - till +30 mV falling phase- Na channels inactivation, high voltage opens also voltage-sensitive K channels – potential towards resting level... and even „overshooting“ it - (after)hyperpolarization
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1 action potential requires high, but limited number of ions - considering the whole cell it is capable of producing many action potentials What keeps the ion distribution appropriate? Each spike is followed by a refractory period. An absolute refractory period - it is impossible to evoke another action potential – during spike and right after it (Na channels are open and after that inactivated) A relative refractory period - a stronger than usual stimulus is required to evoke an action potential (hyperpolarization; part of Na channels recovered)
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airway pressure diaphragm EMG expiratory neuron exp insp expiratory neuron burst extracellular spike waveform Rest # 4
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Propagation of action potential Local current spread (electrotonic conduction) – depolarization of nearby part of membrane
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- without the depression (an energy comes from the cell) along nerve or muscle fibers - a wave (a spot) of electrical negativity on the surface (electrical positivity on the internal site of membrane) due to openning and closing of voltage gated ion channels Propagation of action potential – local currents refractoriness
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Saltatory conduction from one node of Ranvier to the next one orthodromic conduction antidromic conduction
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Electrical stimulation of nerve (muscle) fibers Rheobase - minimal current amplitude of infinite duration (practically a few 100 ms) that results in an action potential (or muscle contraction) Chronaxy (-ie) - minimum time over which an electric current double the strength of the rheobase needs to be applied, in order to stimulate a nerve cell (muscle fiber) anode - higher polarization - lower excitability cathode - depolarization - higher excitability duration of electrical pulse [ms] intensity of current [mA]
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Summary depolarization, repolarization, hyperpolarization action potential – the shape, mechanisms refractory periods propagation of action potential (continual spreading, saltatory conduction) electrical stimulation – rheobase, chronaxy graded potential synapse, neurotransmitter, mechanisms of transmission receptors (ionotropic vs. metabotropic) EPSP, IPSP, summation (temporal, spatial) convergence, divergence
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I will be pleased to take your requests and comments. Please, let me know how to improve the lecture (and lecturer) Thank you for your attention.