Graded potentials and action potentials, Study notes of Medicine

Download Graded potentials and action potentials and more Study notes Medicine in PDF only on Docsity! GRADED POTENTIALS AND ACTION POTENTIALS Near East University Faculty of Medicine Department of Biophysics Dr. Aslı AYKAÇ Nervous System Information travels in one direction Dendrite → soma → axon • Glia – Not specialized for information transfer – Support neurons • Neurons (Nerve Cells) – Receive, process, and transmit information Nervous system cells are comprised of glia and neurons. Neurons are responsible for receive, process, and transmit information in nervous system. These signals occur in two forms: 1. graded potentials 2. action potentials Graded potentials are important in short distances. Action potentials are the long distance signals of nerve and muscle membranes.  Nerve and muscle cells as well as some endocrine, immune, and reproductive cells have plasma membranes capable of producing action potentials. • These membranes – are called excitable membranes. – Their ability to generate action potentials is known as excitability.  All cells are capable of conducting graded potentials, but excitable membranes can conduct action potentials. M e m b ra n e p o te n ti al ( m V ) Time The terms  depolarize  repolarize  hyperpolarize are used to describe the direction of changes in the membrane potential relative to the resting potential. Changes in Membrane Potential Membrane potential (mV) -70 Ex Depolarization Hyperpolarization Repolarization Resting potential • Short-lived, local changes in membrane potential • Decrease in intensity with distance • Their magnitude varies directly with the strength of the stimulus • Sufficiently strong graded potentials can initiate action potentials Graded Potentials Graded Potentials Depolarized region (a) Depolarization (b) Spread of depolarization Figure 11.10 Terms Describing the Membrane Potential Resting membrane potential = resting potential The steady transmembrane potential of a cell that is not producing an electric signal. Action potential A brief all-or-none depolarization of the membrane, reversing polarity in neurons; it has a threshold and refractory period and is conducted without decrement. Threshold potential The membrane potential at which an action potential is initiated. • A small region of a membrane has been depolarized by a stimulus, – Opens membrane channels – produces a potential less negative than adjacent areas. – inside the cell, positive charge will flow through the intracellular fluid away from the depolarized region and toward the more negative, resting regions of the membrane. – outside the cell, positive charge will flow from the more positive region of the resting membrane toward the less positive regions just created by the depolarization. • Thus, it produces a decrease in the amount of charge separation (i.e., depolarization) in the membrane sites adjacent to the originally depolarized region, and the signal is moved along the membrane. • Charge is lost across the membrane because the membrane is permeable to ions through open membrane channels. • As a result, the membrane potential changes decreases by the distance from the initial site. • Because the electrical signal decreases with distance, graded potentials can function as signals only over very short distances. • If additional stimuli occur before the graded potential has died away, these can be added to the depolarization from the first stimulus. This process is termed summation. • Graded potentials are the only means of communication used by some neurons. • They play very important roles in the initiation and integration of long-distance signals by neurons and some other cells. • The mechanisms by which a neuron sorts out its various graded potentials and decides whether to generate an action potential is called integration. • There are many factors which affect integration, including strength of the signal, time course, type of transmission, spike frequency adaptation, accommodation, and threshold;the two main types are temporal and spatial integration. • Neurons communicate over long distances by generating and sending an electrical signal called a nerve impulse, or action potential. Action Potential • When a stimulus applied to the membrane in a resting potential, what happens??? ATP outside inside Disturbed by the stimulus ul • Na+ and K+ channels are closed • Leakage accounts for small movements of Na+ and K+ • Each Na+ channel has two voltage-regulated gates – Activation gates – closed in the resting state – Inactivation gates – open in the resting state Resting State Figure 11.12.1 • Na+ permeability increases; membrane potential reverses • Voltage gated Na+ channels are opened, but K+ are closed • Threshold – a critical level of depolarization (-55 to -50 mV) • At threshold, depolarization becomes self-generating Depolarization Phase • Sodium inactivation gates close • Membrane permeability to Na+ declines to resting levels • As sodium gates close, voltage-sensitive K+ gates open • K+ exits the cell and internal negativity of the resting neuron is restored Repolarization Phase The Action Potential: An Overview • The action potential is a large change in membrane potential from a resting value of about -70 mV to a peak of about +30 mV, and back to -70 mV again. • The action potential results from a rapid change in the permeability of the neuronal membrane to Na+ and K +. The permeability changes as voltage-gated ion channels open and close. Action potentials are rapid, large alterations in the membrane potential during which time the membrane potential may change 100 mV, from -70 to 30 mV, and then repolarize to its resting membrane potential . 37 What is responsible for the change in membrane permeability during the action potential? • Although called “action”potential, it is NOT an active (energy-consuming) event for the cell. • It is purely a passive event. It is due to diffusion of ions! • It is dependent on – ionic electrochemical gradients (Na+, K+) and – the membrane’s permeability. Excitable cells have “fickle(unstable)” cell membranes…they keep changing their permeabilities. What determines the membrane’s permeability at any moment? Answer: GATED ion channels—These allow SIMPLE DIFFUSION of ions down their electrochemical gradients When a stimulus applied in the membrane of the cell Ionic Basis of the Action Potential Voltage gated Na + channels are open immediately, and K + channels open slowly Ionic Basis of the Action Potential Voltage gated Na+ channels close Ionic Basis of the Action Potential  1. PHASE: In the resting state, • The leak channels in the plasma membrane are predominantly those that are permeable to K+ions. • Very few Na+ ion channels are open. • The resting potential is close to the K+ equilibrium potential. • The action potential begins with depolarization of the membrane in response to a stimulus. • This initial depolarization opens sodium channels, which increases the membrane permeability to sodium ions  Phase 2 • More sodium ions move into the cell. • The cell becomes more and more depolarized until a threshold (2) is reached to trigger the action potential. This is called the threshold potential.  Phase 4 • At the peak of the action potential (4), Na+ permeability abruptly decreases and voltage- gated potassium channels open.  Phase 5 • The membrane potential begins to rapidly repolarize (5) to its resting level.  Phase 6 •After the sodium channels have closed, some of the voltage-gated potassium channels are still open, and in nerve cells there is generally a small hyperpolarization (6) of the membrane potential beyond the resting level called the after hyperpolarization. Resting membrane Potential Na+ concentrated on outside. K+ concentrated on inside Depolarization Begins Na+ gates open and Na+ begins to flow rapidly into the axon Depolarization Continues Na+ continues to flow rapidly into the axon K+ gates open and K+ begins to flow slowly out of the axon Depolarization Peaks Na+ channels close and Na+ stops flowing into the axon K+ has only just started to leave the axon Na+ and K+ are now both briefly concentrated on the inside of the axon resulting in the inside being positive relative the outside of the axon Hyperpolarization Begins The Na+ channels close, the Na+ pump forces the Na+ out of the axon, back to where it started. K+ channels start to close. Because positive ions are both concentrated on the outside of the axon, the outside is now more positive than when the axon is at rest. In other words, the inside is more negative than resting. Axon Returns to The Resting State Na+ has been pumped back outside K+ has been pump back inside • Many cells that have graded potentials cannot form action potentials because they have no voltage-gated sodium channels. Different types of action potential Transmembrane potential: E;, — Ey, (mV) Motor neuron p2msec Skeletal muscle jo msec Cardiac ventricle 200 msec Refractory period • Ionic equilibrium returns back to resting potential. • At this stage the cell close to new stimuli. • In the relative period stimuli that reach over threshold level can initiate action potential. • Time from the opening of the Na+ activation gates until the closing of inactivation gates • The absolute refractory period: – Prevents the neuron from generating an action potential – Ensures that each action potential is separate – Enforces one-way transmission of nerve impulses Absolute Refractory Period • Na+ influx causes a patch of the axonal membrane to depolarize • Positive ions in the axoplasm move toward the polarized (negative) portion of the membrane • Sodium gates are shown as closing, open, or closed Propagation of an Action Potential (Time = 0ms) Propagation of an Action Potential (Time = Oms) Sodium gate in Closing Open Closed membrane + + Membrane potential | {a) Time = 0 ms • Ions of the extracellular fluid move toward the area of greatest negative charge • A current is created that depolarizes the adjacent membrane in a forward direction • The impulse propagates away from its point of origin Propagation of an Action Potential (Time = 1ms) Propagation of an Action Potential (Time = 2ms) Closed Closing Open Closed + + + + + + + + QraesO@ + ’ { Y My Y M Lf uy - fy i ' J Distance along the axon (mm) (c) Time = 2 ms • All action potentials are alike and are independent of stimulus intensity • Strong stimuli can generate an action potential more often than weaker stimuli • The CNS determines stimulus intensity by the frequency of impulse transmission Coding for Stimulus Intensity Coding for Stimulus Intensity • Upward arrows – stimulus applied • Downward arrows – stimulus stopped • Current passes through a myelinated axon only at the nodes of Ranvier • Voltage-gated Na+ channels are concentrated at these nodes • Action potentials are triggered only at the nodes and jump from one node to the next • Much faster than conduction along unmyelinated axons Saltatory Conduction Saltatory Conduction EQUILIBRIUM POTENTIALS • Equivalent Electrical Circuit • Nernst Equation • The polarity of each battery is as shown: namely the pole facing inwards is negative for K+ and Cl- and positive for Na+. • These polarities are based on the directions of the concentration gradients and charge on the ions. Nernst Equation • For each ionic species distributed unequally across the cell membrane, an equilibrium potential (Ei) or battery can be calculated for that ion from the Nernst equation. • Ci is the intemal concentration of the ion, • CO is the extracellular concentration, • R is the gas constant (8.3 J/mol.K), • T is the absolute temperature in kelvins (K =273+ᴼC) • ℱ is the Faraday constant (96 500 C/eq), • z is the valence (with sign). • Taking the RT/ ℱ constants and the factor of 2.303 for conversion of natural log (In) to log to the base of 10 (log10) gives: ENa = +60 mV • Because Na + is higher outside (145 mM) than inside (15 mM), the positive pole of the Na+ battery (ENa) is inside the cell. E K =-94 mV • K + is higher inside (150 mM) than outside (4.5 mM), and so the negative pole is inside. ECl= -80 mV • Because Cl- is higher outside (100 mM) than inside (5 mM), the negative pole is inside. Driving force = E m - E i • Thus, in a resting cell, the driving force for Na+ is (Em-ENa)= -8OmV - (+60mV) (Em-ENa)= 140mV • The negative sign means that the driving force is directed to inside for Na+. • The driving force for K + is (Em-EK)= -80 mV- (-94 mV) (Em-EK)= +14 mV The driving force for K + is small and directed to outside. • The driving force for Cl- is nearly zero for a cell at rest in which Cl- is passively distributed. (Em-ECl)= -80 mV- (-80 mV) (Em-ECl)= 0 • In steady state condition, net charge carried by passive flow must be zero. • Therefore at rest or • In a resting cell, Cl- can be neglected, and the Na+ current (inward) must be equal and opposite to the K + current (outward) to maintain a steady resting potential: IK = - INa gK (EM - EK )= gNa (EM - ENa ) In the resting membrane the driving force for Na+ ion is much greater than that for K + , gK is much larger than gNa ,so the currents are equal. Ix = 9x(Em — Ex) Iva = JnalEm _ Ena) > hk + Ina + Te =0 Igy = Gci(Em — Eci) JnalEm — Ena) + 9x(Em — Ex) + Gci'Em — Ei) = 0 When I(=0 Inal(Em _ Ena) + Ix(Em _ Ex) =0 JnalEm ~ Ena) = —9xlEm ~ Ex) Ex + Ena Cm OK om Dia OK