YR1 Lecture 1H - Membranes - Action Potentials - Dr Yossi Buskila 2021 PDF

Membrane potentials & action potentials Dr Yossi Buskila School of Medicine Email – [email protected] 1 Learning Objectives Describe the basic structure of a neuron and its function Describe the structure of the excitable membrane and explain the process by which ion channels generate a...

Membrane potentials & action potentials Dr Yossi Buskila School of Medicine Email – [email protected] 1 Learning Objectives Describe the basic structure of a neuron and its function Describe the structure of the excitable membrane and explain the process by which ion channels generate action potentials. Define the terms resting membrane potential, action potential, threshold, hyperpolarization, depolarization and propagation. 2 Definition of the Nervous system The Nervous system is a complex network of nerve cells and fibers spread throughout the body. Its function is to interpret, store and respond to information received from inside and outside the body. Main in put = Sensory Brain Output = Motor system = CNS command ↳ To muscle fibres 3 Definition of the Nervous system Why do we need the nervous system? Control system ↓ why ? = Sense/response ↳"SURVIVAL" 4 Definition of the Nervous system Why do we need the nervous system? To deal with a changing environment! 5 The nervous system as a control system ↑ Survival" access-response flight/flight ↑ 6 The nervous system as a control system 7 The nervous system as a control system Friend Fight or or Threat Run away 8 The nervous system as a control system Friend Fight or or Threat Run away 9 The nervous system as a control system If Felix wants to keep all of his 9 souls, he needs to use a control system, that is built out of a sensory system that sends information about the environment (Internal and external). Use of control system > - secrory system. 9 8 souls to go 10 The nervous system as a control system The nervous system is a control system, in which we perceive changes in the internal and external environments, assess the situations and react to them. "Control system" General structure of the nervous system Sensory system Input Processing system Output Action 11 The nervous system as a control system General structure of the nervous system Environment Sensory system Input Processing system Output Reaction Motor system 12 The building blocks of the nervous system The human nervous system is made out of two types of cells: Neurons and Glia Humans have about a 100 billion neurons in the brain, and roughly the same amount of glia (1 to 1) - Ratio Neurons A neuron is the functioning cellular unit of the nervous system that specialized to receive, integrate, and transmit information through electrical and chemical means. There are many types of neurons, however: All neurons share the same basic structure ende o typePolar & ↑ ② small Soma ② Motor branche -all ② single neurnose - layer cortex). body fibre Dendrites Axon 13 Cellular anatomy of the nervous system (MAIN CELL) control synaptic activity brainwaves etc Very active Glia Astrocyte Come from the word ‘glue’ in Greek, and till recently were considered only as supporting cells for the neurons, however recent studies indicate that they also involved in modulating synaptic activity and regulate the processing of neural signals. (Gva) cell in -. = > - Four types of glial cells - Periplay NS main. eve - Oligodendrocytes & Schwan cells – provide insulation for neurons (myelin sheath) at the CNS and PNS. NEURONES Astrocytes – most prevalent type of glia in the CNS. Modulate synaptic activity; take part in isolation forming the BBB; regulate blood flow and ions ~ brain CNS in the * blood vessels transmission to the brain. different to me rest CNS DV in whole body dy ,of. Microglia – take part in the immune system (acts ↓ like macrophage) BBB ; Special brain ↑ * a - are structure in astrocytes ↑ which Ependymal cells – Involved in the production form gapped Brain (cover) into components of the cerebrospinal fluid (CSF) and tight junction get restrict Bu neuroregeneration lemen of ventricles brain from , -. to.. 14 The basic structure of the Neuron *Dendrites– short, branching fibers extending from the soma. Receiving incoming information. Flow of Information O > - CELL FACTORY Soma – cell body, contains the nuclei, ribosomes and more. It is the site of major metabolic activity in the neuron Axon– singular fiber that carries information away from the soma to the synaptic sites of other TERMINALS neurons, muscles or glands. STOMA > - INFOM of AXON (SC) Axon terminals (pre-synapse)– are the presynaptic connections between two neurons or between a neuron and a muscle or gland. 15 The basic structure of the Neuron Although all neurons have the same basic structure (Dendrites, Soma, Axon), they can have different morphologies! 16 Morphological Classification of Neurons Multipolar Neurons – one axon with many dendrites (most common) Bipolar Neurons – one axon with one dendrite (sensory neurons) Unipolar Neurons – Single axon that branches to peripheral axon and central axon. They have specialized dendrites which respond to a specific sensory modality act like axon sustim e do iraputid out - Most - common wit a mullple dendrites 17 Neuronal communication How neurons communicate? 18 Communication through electrochemical signals Neurons communicate through electrochemical signals. To understand the nature of communication in the brain, one must look into the mechanisms governing the neuron’s excitable membrane 19 Membrane structure and function The cell membrane surrounds the cytoplasm of living cells, physically separating the intracellular components from the extracellular environment consists of phospholipid bilayer with embedded proteins ( - different expressions of certain channels ↳ SOMA Defined as the potential difference, measured in mV, across a cell membrane. Usually the membrane potential of a neuron is around -65 mV. We refer to the membrane potential as isopotential, although minor differences between compartments do occur. 24 Membrane potential: The membrane potential is measured by inserting a microelectrode through the cell membrane and measuring the voltage of the interior relative to the exterior of the cell. Testing : ↳ change in a cell outside Reference electrode electrode 25 Membrane potential: The membrane potential is determined by the relative fluxes of Na+, K+ and Cl- ions through specific ion channels in the cell membrane equalBOTH led side - If on to in lead chang the electricial potential t No (( ↑ This Rost potentid 65 E - - I chloride Sodium Cove potassim protein - Large charge. 26 Membrane potential: Resting membrane potential depends on the relative conductance (or permeabilities) of the membrane to major ions, and on the equilibrium potential for these ions. ~ for each of the jons ) The equilibrium potential (Ei) is the membrane potential at which the net influx of a certain ion through the membrane is zero. At the ion equilibrium potential, its electrical gradient is equal and opposite to its chemical concentration gradient and therefore there is no net ionic flow across the membrane. It is the ion “battery”, and the ions will always move towards their (Ei). ( E charged molecule K+. ④ = -90 mV ENa+ = +47 mV Ecl- = -60 mV ! CELL - 90 - MEMBRANE) not resting - because the ion are kt not still at equilibrium. Electrical force [K+]o = 3 mM Net current [A-]o = 0 mM [K+]i = 80 mM Chemical force ⑦ [A-]i = 116 mM Vm = -95 mV 27 Membrane potential: What happens when the membrane is permeable to more than one ion? Interior of cell is ~ -65 mV relative to the exterior * In order to get resting to potential ; mainly eve - potassium chloride need & Sodium be at Electrical force equilibriu to , Vm = -65 mV Chemical force. ↳ 765 (alments) How the resting membrane potential stays at -65mV? The membrane potential is maintained through active transport of Na+ and K+ via the Na-K pump SODIUM-POTASSIUM PUMP. 28 Membrane potential: The Na+/K+ pump is electrogenic. Transfer 3 Na+ ions out of the cell and 2 K+ ions into the cell Requires ATP different is a There * & of sodium OUTSIDE ↓ charge > Constanly providing a O harge into the the concentration inside cell ↓ electrogenetic ~ cell. K + OUTSIDE + INSIDE ↑ A. Sodium will always try to reach equilibr 29 Neurons are excitable cells: (polarisation) What does “excitable cell” mean? -Resting have membrane +65) can ( potential that. be modified - - we G Their resting membrane potential can be modified by excitatory or inhibitory signal arriving from other neurons - ) probabilit to initiate. potential action ↑ toward action. potential Excitation moves the resting membrane potential towards 0 mV (depolarization) and increase the probability to fire an action potential I> of action potential inhibitory Inhibition makes the resting membrane potential more negative (hyperpolarization) and decrease the probability to fire an action potential 0 Membrane potential (mV) In general: -30 -60 - 65 -90 I ↑ more going ↳ U O toward polarisation ↓ of -65 Resting membrane potential ↓ Depolarization Hyperpolarization Away from 0 mark = polarization ↑ 1 ↑ O Time (msec) 30. Neurons are excitable cells: Neurons are excitable cells: What is the mechanism that drive the membrane excitability? Voltage gated channels - Voltage alterations activates voltage-gated ion channels, which are ion selective (Na+, K+ or Cl-) SODIUM & potas ium (selectivel Cit. * Once the channel is open, ions will pass through (inside/outside of the cell) according to their equilibrium potential. As these ions are electrically “charged”, they carry that electrical charge with them and thus change the membrane potential. 31 Neurons are excitable cells: ISPS = Inhibitory P/s OR potential (excitator. potential ) P/S. EBSB. negatively charged During depolarization, more positive charge (Na+; Ca2+) get into the cell (or negative charge leave the cell) chloride -> is Na+; Ca2+ & Cl- electrical recording. Depolarization = post-synaptic signals During hyperpolarization, more negative charge get into the cell (or positive charge leave the cell) signals potentials. Dendrites Cl- Hyperpolarization st mas · K+ 32 Neurons are excitable Neurons are excitable cells: cells: Once the depolarization pass the firing threshold, the neuron generates action potentials Action potentials are brief (~1 ms) reversals of the membrane potential, in which the membrane rapidly depolarizes and then repolarizes Evey Action potential has ② depolarising phase. ② Repolarising phass # -> 3 Covershoot. pleases Ge ④ O. covershoot) I I hyperpolarisation Because action potentials are triggered by the opening of voltage-gated ion channels, they can be evoked by an external or internal voltage or current after. 3 O. Then goes base line. / &2-2miliseconds) time ii - i ( to 8 -65. 33. Neurones are excitable Neurons are excitable cells: cells: PASS THE - not evey depolariation will has an action depolarisation - Action potentials follow the “All or None" principle - the neuron either does not reach the threshold or a full action potential is fired. Hence, all action potential’s (spikes) of the same neuron will be similar. ↓ ↳ NO ACTION POTENTIAL Suprathreshold current - - Once ACTION POTENTIAL (piquant) Injecting currents in the ⑦ the current/density Initiate action paned ↳. potential ↑ Subthreshold current Tate the cells. YOU HAVE A ACTION POTENTIAL potential Ways to measure the action potential (spike) threshold / & Brown #Blue current density leads to THRE SHOLD all amplitude ↑. ↳ similar ④ op 6-7 action potentials.. 34 Neurons are excitable cells: What is the mechanism that leads to an action potential? 35 Resting membrane potential “it’s the squid that really ought to be given the Nobel Prize” Hodgkin, A.L., 1973 Alan L. Hodgkin and Andrew F. Huxley first to record resting membrane potential and action potential from living neuron using an amplifier at 1939 Used squid giant axon (0.5 mm in diameter) 36 Neurons are excitable cells: According to Hodgkin & Huxley, much of the change in membrane potential during an action potential can be explained by the Na+ current Rep depolarisation phase > - due to the responsible delayed It conductance short 4) After) recession/under the sodium conductance is the 1st conductance & similar thatLacpotential ↳ MAJOR CONDUCTANCE That responsible for DEPOLARISATON. 37. Action potentials propagate along axons Action potentials are initiated in a special zone called the Axon hillock, and propagate along the axon all the way to the axon terminals.> because of the concentration of Sodium channels around the Chigher than other area. region of the cell). Why action potentials are initiated at the Axon Hillock? Because the density of Na+ channels in the Axon Hillock is very high! 38 Action propagate along axons Actionpotentials potentials propagate along axons: Why do we need action potentials? What are they good for? mits > - ALL or NONE (binary 2 On things one , Reliability and fast transmission of signals ↳ Trand very. fast > - important LONG PROCESS) DIfFUSION MEARS) ↑ can reurones in the 11 NS m be Long). The axons in the peripheral nervous system are long, requiring rapid transmission of electrical signals 39 Action potentials propagate along axons How does action potentials propagate along axons? becay Length - ing constant) with time = no action potential , shape (Theshold) remained the came Reliabilitignal of the 40 Action potentials propagate Action potentials propagate alongalong axonsaxons: OPEN How does action potentials propagate along axons? regenerate sodium across & the currents potassium membrane The ionic fluxes occur along the whole length of the axon in regenerative fashion changing the membrare channel ↓ potential propagate along Action currents I > - > - ↳ also going across channel & across currents - changing the ↑. membrane below the cell membrane unmyelinated axou X-oligodendrocytes ① schwann cell them that installating ↳ Conduction) Velocity = FAIRLY SLOW volted > - 1 m/per gated channels acros all the axous second Action potentials that propagate along unmyelinated axons conduct slowly (~1 m/s) 41 Action potentials propagate Action potentials propagate alongalong axons axons: As spikes regenerate at every point along the axon, it can be time consuming To increase the spike velocity, some axons are covered with myelin sheath The ionic fluxes associated with the action potentials occur only at the nodes of Ranvier - the gaps in the insulating myelin sheath have Most names of invigoration cells ② ↑ 1 fastest neurona we hay in myelin our sheets Schwann cells (NS) ↳ coming from either or oligodentrocyte. & insulation - ↑ speed of propag ation the · velocity of propagation velocity 120 m/sev - Instead of potential ess action - getting calk step regenerated along the Action potentials that propagate along myelinated axons travel fast (~80 m/s) in "Nods of Gaps are called Ranvier" & only me - in regenerated getting the between myelin gaps sheets. a 42 Action potentials propagate Action potentials propagate alongalong axons axons: along ranveer mode the DISTRIBUTION OF SOME CONDUCTANCES Action potentials “jump” from one node to the next, in a manner termed saltatory conduction There are voltage-gated channels within the membrane that allow sodium or potassium ions through * mode o Nat Nap Ks ATP Na+ K+ ranzin Ih Na+ Lk Ks Kf Ca2+ Na+ K+ Kf Na+ 43 Action potentials propagate Action potentials propagate alongalong axons axons: Conduction velocity is higher in large diameter axons The fastest conducting myelinated axons in the human body are the sensory axons from mechanoreceptors in the skin and muscles (~80-120 m/s) The unmyelinated sensory axons, which convey heat and pain information, are the slowest (~1 m/s) ↑ the diameter , the ↑ the conduction - Propagate inacity. activity. 44 Action potential “Refractory period” Action potentials propagate Action potentials refractory periodalong axons: Following a spike, the excitable membrane will enter to a refractory period, during which the threshold to initiate a second spike in increased I Doesn't me do matter what how much into the * cell= S Sets the the a another action - stimlas Isn't action inject generate dus to inactiviation sodium potential not elicit can The refractory period is divided to relative and absolute an of channels. potential L. ↓ CAUSE d Sodium can not get The inside cell & therefore upper fining frequency of cell cannot limit of the an Q elicit action potential mactivation of the , ② activation Delayectchannels. potassium to of& sodium channel be might action an generate but -> potentialmuch able We , · to injectto stimulation those two , we bigger 45 overcome things need Action potential “Refractory period” Action potentials propagate Action potentials refractory periodalong axons: changes is shaps & amplitudes e Refractory period. When vanished ↳ Absolute retractory period , when it's the time duringaction. when Test = ② ② > -. potential One stimula Second stimulas after a while lookingatthe action 46 Action potential “Refractory period” Action potentials propagate Action potentials refractory periodalong axons: damp. Experiment I voltage The main effectors on the refractory period are: Absoluteperiod Refractory activationchannels -no 1) inactivation of Na+ channels 2) Delayed increase in K+ conductance. - k + LEAVES cell signal down that O - Lsignal - Outward current ④ If the meaning the Ista is of sodium - currents that through Can members in-ward current OCTWARD. CURRENT K+ conductance or - that's recorded. ↳ Sodium. current ④ -all ↑ decrease is 7 - recorded goes level below the baseline Current ↳ toward * - the cell is. going - cell. Above the baseline ↳ ④ current LEAVES the cell go a. 47 Action potential “Refractory period” Action potentials propagate Action potentials refractory periodalong axons: Summary – Refractory period For a short period after the passage of a spike, the threshold for stimulation is raised, such that if a neuron is stimulated twice in quick succession, it may not respond to the second stimulus. The inactivation of Na+ channels and the delayed increase in K+ conductance are the underlying ionic conductance's which can explain the refractory period. The absolute refractory period is the brief interval after a successful stimulus when no second stimulus, however maximal, can elicit another response. The absolute refractory period is followed by the relative refractory period, during which a second response can be obtained if a strong enough stimulus is applied. 48 Action potential “Refractory period” Action potentials propagate Action potentials refractory periodalong axons: The refractoriness of a nerve after conducting an impulse sets an upper limit to spike frequency. The maximal frequency at which an axon can conduct impulses is limited by the absolute refractory period of the axon (~1 ms), within which the axon is inexcitable The absolute refractory period for myelinated axons is ~1 ms, for unmyelinated axons it is ~2 ms 49 Actionpotentials potential “Refractory period” Action propagate along axons: Summary Resting membrane potential is maintained by active processes: the Na+-K+ pump acts to keep the extracellular concentration of Na+ high, thereby maintaining a high chemical gradient across the membrane An action potential is a transient reversal of membrane potential, due to the influx of Na+ during the opening of voltage-gated Na+ channels Action potentials are self propagating, with conduction being faster in myelinated than unmyelinated axons. The propagation velocity of action potentials is directly proportional to axonal diameter 50 Action potential “Refractory period” Action potentials propagate along axons: Further reading Textbooks 1. “Neuroscience: Exploring the Brain” by Bear, Connors, and Paradiso. 2. “Physiology of behavior” by Neil R Carlson. 51