Adobe Systems 1 MEMBRANE OF EXCITABLE CELL. ELECTRICAL TRANSMISSION OF INFORMATION. Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 2 ligand hydrophilic glycocalyx ion hydrophobic I – integral protein R – receptor E – enzyme K – channel (kanál) P – pump (ATP-ase) Membrane molecules Protein molecules PLASMATIC MEMBRANE membr21 Nexus (gap junction) Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 3 SODIUM-POTASSIUM EXCHANGER Na-K-pumpa rest2_ RESTING MEMBRANE POTENCIAL It is the result of: different cell membrane permeability for sodium (Na +) and potassium (K+) ions the presence of a sodium-potassium pump in cell membranes, which promotes this uneven distribution of intracellular and extracellular fluid ions ü Phenomena occurring in the resting membrane potential üLow membrane permeability for Na+ üHigh membrane permeability for K+ üPrimarily active transport: Na+ out of the cell and K+ into the cell (given by the presence of Na+-K+ ATPase, in the ratio: 3 Na + out / 2 K + inwards ) üInside the cell remain anions of proteins and phosphates • (thanks to this, we measure the electrical voltage between the outside and the inside of the cell) We conclude that: The cell membrane is POLARIZED at rest Adobe Systems Marie Nováková Department of Physiology Faculty of Medicine, Masaryk University 7 3 2 ATP ase Na+ K+ 150mM 155mM + + + + + + + + + + + + + + + + + - - - - - - - - - - - - - - - - - - - - - - - - Na+ K+ Concentration gradient Electrical gradient Nernst equation: Ex = R . T (Cxout) F (Cxin) ln ENa = +40 mV EK = -90 mV ECl = -70 mV ECa = +60 mV Ix = gx . (E - Ex) I – current, E – voltage, g – specific voltage and time-dependent conductance RESTING MEMBRANE VOLTAGE Er = -85 mV Equilibrium potential •For individual ions, we are able to calculate the so-called ions EQUILIBRIUM potential according to NERNST EQUATION • •In this context, potassium is most talked about, since its equilibrium potential is closest to the value of the resting membrane potential • (Ek+ = -70mV) •Ek+ – equilibrium potential of potassium means that the force driving the diffusion K+ outwards (chemical gradient) is just as great as the force of the potential acting in the opposite direction (electrical gradient) •for sodium: ENa= + 40mV Physiological significance of resting membrane potential •Cells use it to regulate their physiological functions, which include: –permeability of membranes of muscle and nerve cells for ions –intracellular calcium release for muscle contraction –release of nerve neurotransmiters (mediators) in the nervous system Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 10 ACTION POTENTIAL Concentration gradient Electrical gradient + + + + + + - - - - - - - - - + + + + - - - - - - - - + + + + + + + - - - - - Na+ gNa K+ (E-EK) Depolarisation Transpolarisation Repolarisation (Hyperpolarisation) Resting membrane potencial: •In the cell membrane at rest condition •Inside the cell - negative charge, positive charge on the cell surface 0 1 2 0 + - +20 až 30 mV 0 mV -55 mV treshold -90 až -70 mV Time (ms) •cell is impermeable to Na+ •inside the cell there is a higher concentration of K+, outside the cell there is a higher concentration of Na+ •the concentration of K+ inside is less than the concentration of Na+ outside ® negative charge inside the cell Action potencial Resting membrane potential and action potential Action potencial (AP) •If the voltage threshold (-55 mV) is exceeded, an action potential is generated on the membrane • •Depolarization phase •Na+ channels open •Na+ enters the cell •Law „All or nothing“ – if the threshold is not exceeded, no AP, if the threshold is exceeded – the AP is created 0 1 2 0 + - +20 až 30 mV 0 mV -55 mV práh -90 až -70 mV Resting membrane potential Action potential Resting membrane potential time (ms) •Repolarization phase •Na+ channels are closed again (very fast inactivation) •K+ channels are open-eflux of potassium •Na+ is pumped out, K+ is pumped in •Voltage gets back to rest values Resting membrane potential Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 13 Figure1 1 Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 14 50mV -100 -50 0 Threshold potential Resting potential transpolarisation depolarisation repolarisation influx of sodium eflux of potassium ACTION POTENTIAL hyperpolarisation •Unit of excitation activity •„All or nothing“ response •Propagation without decrement („domino effect“) •Refracterity Local current + - depol. pol. Propagation with decrement membr21 ACTION POTENTIAL (AP) •By irritating excitable cells (muscle or nerve), resting membrane potential can turn into ACTION potential • •AP is created according to the law: "all or nothing„ • - a sufficiently strong stimulus (the so-called overtreshold stimulus) is needed for its creation •- its further spread takes place without losing its size • • Physiological significance of action potential •by changing the resting membrane potential into an action potential, the following occurs: •encode and transmit information in living systems (nervous system) •muscle contraction (musculature) is triggered Morphology of the skeletal muscle fiber sarcomere Z disc M disc actin filament I band H zone A band myosin filament myosin heads Motor end-plate mitochondria nicotinic receptors Plasma membrane myelin Schwann cell cytoplasm Axon of the a-motoneuron Terminal button Vesicle of acetylcholine Muscle fiber Excitation – contraction coupling Excitation •Action potential (AP) spreads on axon from alfa-motoneuron to neuro-moto end-plate •Release of acetylcholine from vesicles to synaptic cleft •Binding of acetylcholine with the nicotinic receptors placed on post-synaptic membrane •Opening of Na+ channels (connected with acetylcholine receptors) and intake of Na + •Local depolarization of the membrane •Opening of voltage gaited channels for Na + •Formation of action potential AP Sarcoplasmic reticulum Sarcolemma cytoplasm Ca2+ Sarcoplasmic reticulum DHPR RYR1 T-tubule Contraction •Spreading of action potential (AP) across fiber and into transversal tubule (T-tubule) •Dihydropyridine receptors (DHPR) in the membrane changes its conformation •Interaction of DHPR with ryanodine receptors (RYR1) in the membrane of sarcoplasmic reticules •Opening of calcium channels in the sarcoplasmic reticulum and intake of Ca2+ into cytoplasm •Binding of Ca2+ with troponin C •Binding of myosin heads on actin •If enough of Ca2+ and ATP in cytoplasm, myosin shifts along actin ® contraction of muscle • Contraction ends with decrease od Ca2+ concentration in the cytoplasm (Ca2+ is pumped by Ca-ATPase into the reticulum) Rigor mortis – caused by ATP deficit ® formation of strong link between actin and myosin AP Sarcoplasmic reticulum sarcolemma cytoplasm Ca2+ Sarcoplasmic reticulum DHPR RYR1 T-tubule Excitation – contraction coupling Cardiac muscle Skeletal, cardiac and smooth muscle – action potential and contraction Skeletal muscle Smooth muscle Action potential (AP): approx. 250 ms Contraction: approx. 250 ms 0 200 100 300 400 Time from AP onset (ms) AP: approx. 5 ms Contraction: approx. 20 ms AP: approx. 50 ms Contraction: approx. 1000 Fluctuating resting membrane potential Long refractory time AP duration depends on heart rate Duration of the electro-mechanical latency and contraction depends on the fiber type (F or S) spike Propagation of action potential (unmyelinated fiber) AP spreads through the axon away from the neuron's body The action potential (AP) arises in the initial segment of the axon If the initial depolarization does not exceed the voltage threshold, AP does not occur If the initial depolarization exceeds the stress threshold, AP arises and propagates further through the axon depolarization Propagation of AP (nonmyelinated fibre) AP Propagation of AP (nonmyelinated fibre) Propagation of AP (nonmyelinated fibre) Propagation of AP (nonmyelinated fibre) Propagation of AP (nonmyelinated fibre) AP spreads without decrement (without loss), ie. The AP is still the same size Because the AP is still the same size, the transmitted information is encoded in the AP frequency Propagation of AP (nonmyelinated fibre) Resting membrane potential Propagation of AP (myelinated fibre) Formation of AP in the initial segment of the axon Propagation of AP (myelinated fibre) The AP jumps the myelin sheath to node of Ranvier Propagation of AP (myelinated fibre) … And to another node of Ranvier… Propagation of AP (myelinated fibre) … And to another node of Ranvier… Propagation of AP (myelinated fibre) …and to another node of Ranvier… Saltator jumping of AP - faster (unmyelized fibers lead AP more slowly) Propagation of AP (myelinated fibre) Adobe Systems LOCAL RESPONSE of MEMBRANE POTENTIAL ̶evolutionarily older type of membrane reaction to irritation ̶we find it in lower animals, but also in the human nervous system it has its function ̶its properties (unlike AP): ̶depends on the intensity of the stimulus ̶spreads with decrement ̶refractery period is absent ̶ e.g.: we find it as a reaction to irritation of sensory cells –“ receptor potential“, mainly on the synapses of our NS (postsynaptic potencial – excitatory-inhibitory), endplate potential in neuromuscular junction ̶ Definujte zápatí – název prezentace nebo pracoviště 36 https://oerpub.github.io/epubjs-demo-book/resources/1224_Post_Synaptic_Potential_Summation.jpg Synapses - axon The synaptic end of the neuron is also on the muscles (neuromotor plate) or on the glands Synaptic endings Synaptic contact to initial segment Synapses - synapses Axo - somatic Axo - dendritic Synapses – in general presynaptic membrane postsynaptic membrane (neuron, gland, muscle) specific receptor axon Vesicles approach the membrane and release the mediator into the synaptic cleft Incoming of action potencial Examples of neuromediators: Acetylcholin, norepinephrin, dopamin, serotonin, GABA,… Synapses – in general Binding the neuromediator to receptors Binding the neuromediator to receptors triggers sequence of other plots on the postynaptic membrane •Opening of ion channels for: •Ca2+, Na+ ® membrane depolarization •Cl-, K+ ® membrane hyperpolarization •contraction of muscle (neuromuscular junction) •Secretion of substances (in glands) •Changes of metabolism, etc.…… Possible happenings caused by the establishment of a synaptic mediator: Synapses - in general The neuromediator is then very quickly "cleaned" from the synaptic cleft in various ways after its release clearing the mediator back to the synaptic end deactivation and decomposition of the mediator Synapses – in general Neuromuscular junction mitochondria postsynaptic invagination N – cholinergic receptors sarcolemma Myelin sheath membrane of Schwann cell sarcoplasma Axon of a-motoneuron (motor nerve fibre) synapses synaptic vesicles containing acetylcholine Skeletal muscle fibre Acetylcholine is deactivated by acetylcholinesterase and broken down into acetyl and choline Neurotransmitters bound to certain types of receptors of the postsynaptic membrane cause ion channels to open and ions to move from/to the cell ® change of potentials on the postsynaptic membrane ® creates postynaptic potential Receptor with neurotransmitter Ion channel Postsynaptic potencial •is weak (many times weaker than AP) •spreads from synapse with decrement (loss) – shrinks as it distances itself from the synapse (gradually disappears) Postsynaptic membrane Ion Postsynaptic potencial (PSP) AP Postsynaptic potencial inducing cell depolarization (but much weaker than AP) Cation input to a cell (e.g. Ca2+ or Na+) Na+ Na+ Receptor s navázaným neurotransmiterem Iontový kanál Postsynaptická membrána čas (ms) napětí (mV) -90 0 2 4 6 -70 One type of neurotransmitter binds to one type of receptor and opens one type of ion channels E.g. nicotine receptor-bound acetylcholine causes the Na+ channel to open and the Na+ to enter the cell Excitatory postsynaptic potencial (EPSP) Postsynaptic potencial inducing cell hyperpolarization Anion input to a cell (e.g. Cl-) or cation output from a cell (K+) Cl- Cl- Receptor with neurotransmitter Ion channel Postsynaptic membrane time (ms) voltage (mV) -90 0 2 4 6 -85 Inhibitory postsynaptic potencial (IPSP) One type of neurotransmitter binds to one type of receptor and opens one type of ion channels E.g. GABA bound to GABA A causes the CL- channel to open and the CL- to enter the cell Spread EPSP PSP •Is weakly than AP •Spread with decrement (with loss), gradually disappears dendrit Soma of neuron EPSP spreding across dendrit axon Action potencial Excitatory synapses dendrit neuron IPSP spreading after dendrit axon AP Inhibitory synapse Spread IPSP Summation of postsynaptic potencials There may be both excitatory and inhibitory synapses on the neuron's body - EPSP and IPSP - add up •Predominance of IPSP – hyperpolarization of membrane •Predominance EPSP – depolarization of membrane dendrit neuron axon AP Excitatory synapse EPSP axon inhibitory synapse AP čas (ms) napětí (mV) -90 0 2 4 6 -70 IPSP EPSP IPSP EPSP and IPSP that originated on dendrits at the same time Summary dendrit neuron axon EPSP spreading after dendrit Incoming AP Excitatory synapse IPSP spreading after dendrit inhibitory synapse There may be both excitatory and inhibitory synapses on the neuron's body - EPSP and IPSP - add up dendrit neuron axon Action potencial Excitatory synapse EPSP Excitatory synapse Action potencial čas (ms) napětí (mV) -90 0 2 4 6 -70 EPSP EPSP Two EPSP that originated on dendrits at the same time Summary Summation of postsynaptic potencials dendrit Neuron´s body Incoming AP excitatory synapse treshold -55 Increasing of summary PSP IPSP Action potential time(ms) voltage (mV) -90 0 2 4 6 -70 inhibitory synapse inicial segment of axon AP EPSP EPSP IPSP All EPSP and IPSP that came to the neuron at the same time add up. If the sum of all PSP exceeds the threshold (around -55mV), the action potential is created. treshold -55 Summation of PSP IPSP Action potencial time (ms) voltage (mV) -90 0 2 4 6 -70 Inicial segment of axon EPSP – has different amplitudes, but is smaller than the amplitude of action potential, spreads with decrement Action potential – it arises only after crossing the threshold, has a constant amplitude, spreads without decrement Membrane depolarization may not lead to AP If the depolarization does not exceed the threshold, the AP does not create Summation of postsynaptic potencial time (ms) voltage (mV) -90 0 2 4 6 -70 EPSP treshold -55 Action potential Space summation The more excitatory synapses on the neuron, which the AP came up with at the same time, the more EPSP was created and the easier it was to reach the threshold for the formation of AP on the postsynaptic neuron Inicial segment of axon Incoming AP Created of AP EPSP The higher the frequency of AP coming to synapses, the greater the summation of PSP and the sooner the AP threshold on the postsynaptic neuron is reached Time summation Postsynaptic neuron Presynaptic neuron time(s) voltage (mV) -90 -70 individual EPSP individual EPSP Summation of PSP treshold Action potencial Incoming AP Created of AP Incoming AP – presynaptic membrane neuron7083.jpg •Coding – intensita of stimulus recorded by the receptor is recoded to AP frequency •Decoding – on synapses - frequency of AP is transformed into PSP •Recoding - if the sum of all PSP exceeds the threshold, creates AP Coding information Převzato z: Atlas fyziologie člověka, S. Silbernagl coding decoding recoding stimulus treshold treshold Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 58 ligand hydrophilic glycocalyx ion hydrophobic I – integral protein R – receptor E – enzyme K – channel P – pump (ATP-ase) Membrane molecules Protein molecules ELECTRIC SYNAPSES membr21 Nexus (gap junction) Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 59 •RESTING MEMBRANE POTENTIAL IS A CONDITION OF EXCITABILITY •IT DEPENDS ON HIGH RESTING MEMBRANE CONDUCTIVITY FOR POTASSIUM ACTION POTENTIAL IS A PROPAGATED ELECTRICAL SIGNAL GENERATED BY FAST SODIUM CURRENT INTO THE CELL Adobe Systems Marie Nováková, Department of Physiology, Faculty of Medicine, Masaryk University 60 •ACTION POTENTIAL REPRESENTS UNIT OF INFORMATION •CODING OF INFORMATION IN THIS SYSTEM IS PERFORMED BY CHANGED FREQUENCY OF ACTION POTENTIALS