Y khoa, y dược - Fundamentals of the nervous system and nervous tissue: Part B

11 Fundamentals of the Nervous System and Nervous Tissue: Part BNeuron FunctionNeurons are highly irritableRespond to adequate stimulus by generating an action potential (nerve impulse) Impulse is always the same regardless of stimulusPrinciples of Electricity Opposite charges attract each otherEnergy is required to separate opposite charges across a membraneEnergy is liberated when the charges move toward one anotherIf opposite charges are separated, the system has potential energyDefinitionsVoltage (V): measure of potential energy generated by separated charge Potential difference: voltage measured between two pointsCurrent (I): the flow of electrical charge (ions) between two pointsDefinitionsResistance (R): hindrance to charge flow (provided by the plasma membrane)Insulator: substance with high electrical resistanceConductor: substance with low electrical resistanceRole of Membrane Ion Channels Proteins serve as membrane ion channelsTwo main types of ion channelsLeakage (nongated) channels—always openRole of Membrane Ion ChannelsGated channels (three types):Chemically gated (ligand-gated) channels—open with binding of a specific neurotransmitterVoltage-gated channels—open and close in response to changes in membrane potentialMechanically gated channels—open and close in response to physical deformation of receptorsFigure 11.6(b) Voltage-gated ion channels open and close in responseto changes in membrane voltage.Na+Na+ClosedOpenReceptor(a) Chemically (ligand) gated ion channels open when theappropriate neurotransmitter binds to the receptor,allowing (in this case) simultaneous movement of Na+ and K+.Na+K+K+Na+Neurotransmitter chemicalattached to receptor ChemicalbindsClosedOpenMembranevoltagechangesGated ChannelsWhen gated channels are open:Ions diffuse quickly across the membrane along their electrochemical gradientsAlong chemical concentration gradients from higher concentration to lower concentrationAlong electrical gradients toward opposite electrical chargeIon flow creates an electrical current and voltage changes across the membraneResting Membrane Potential (Vr)Potential difference across the membrane of a resting cellApproximately –70 mV in neurons (cytoplasmic side of membrane is negatively charged relative to outside)Generated by:Differences in ionic makeup of ICF and ECF Differential permeability of the plasma membraneFigure 11.7VoltmeterMicroelectrodeinside cellPlasmamembraneGround electrodeoutside cellNeuronAxonResting Membrane PotentialDifferences in ionic makeupICF has lower concentration of Na+ and Cl– than ECFICF has higher concentration of K+ and negatively charged proteins (A–) than ECFResting Membrane PotentialDifferential permeability of membraneImpermeable to A–Slightly permeable to Na+ (through leakage channels)75 times more permeable to K+ (more leakage channels)Freely permeable to Cl–Resting Membrane Potential Negative interior of the cell is due to much greater diffusion of K+ out of the cell than Na+ diffusion into the cellSodium-potassium pump stabilizes the resting membrane potential by maintaining the concentration gradients for Na+ and K+Figure 11.8Finally, let’s add a pump to compensate for leaking ions.Na+-K+ ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential.Suppose a cell has only K+ channels...K+ loss through abundant leakagechannels establishes a negativemembrane potential. Now, let’s add some Na+ channels to our cell...Na+ entry through leakage channels reducesthe negative membrane potential slightly. The permeabilities of Na+ and K+ across the membrane are different.The concentrations of Na+ and K+ on each side of the membrane are different.Na+(140 mM )K+(5 mM ) K+ leakage channelsCell interior–90 mVCell interior–70 mVCell interior–70 mVK+Na+Na+-K+ pumpK+K+K+K+Na+K+K+KNa+K+K+Na+K+K+Outside cellInside cellNa+-K+ ATPases (pumps) maintain the concentration gradients of Na+ and K+across the membrane.The Na+ concentration is higher outside the cell.The K+ concentration is higher inside the cell.K+(140 mM )Na+(15 mM ) Membrane Potentials That Act as SignalsMembrane potential changes when:Concentrations of ions across the membrane changePermeability of membrane to ions changesChanges in membrane potential are signals used to receive, integrate and send informationMembrane Potentials That Act as SignalsTwo types of signalsGraded potentials Incoming short-distance signalsAction potentials Long-distance signals of axonsChanges in Membrane PotentialDepolarizationA reduction in membrane potential (toward zero)Inside of the membrane becomes less negative than the resting potentialIncreases the probability of producing a nerve impulseFigure 11.9aDepolarizing stimulusTime (ms)InsidepositiveInsidenegativeRestingpotentialDepolarization(a) Depolarization: The membrane potentialmoves toward 0 mV, the inside becoming less negative (more positive). Changes in Membrane PotentialHyperpolarizationAn increase in membrane potential (away from zero)Inside of the membrane becomes more negative than the resting potentialReduces the probability of producing a nerve impulseFigure 11.9bHyperpolarizing stimulusTime (ms)RestingpotentialHyper-polarization(b) Hyperpolarization: The membranepotential increases, the inside becomingmore negative.Graded PotentialsShort-lived, localized changes in membrane potentialDepolarizations or hyperpolarizationsGraded potential spreads as local currents change the membrane potential of adjacent regionsFigure 11.10aDepolarized regionStimulusPlasmamembrane(a) Depolarization: A small patch of the membrane (red area) has become depolarized.Figure 11.10b(b) Spread of depolarization: The local currents (black arrows) that are created depolarize adjacent membrane areas and allow the wave of depolarization to spread.Graded PotentialsOccur when a stimulus causes gated ion channels to openE.g., receptor potentials, generator potentials, postsynaptic potentialsMagnitude varies directly (graded) with stimulus strength Decrease in magnitude with distance as ions flow and diffuse through leakage channelsShort-distance signalsFigure 11.10cDistance (a few mm)–70Resting potentialActive area(site of initialdepolarization)(c) Decay of membrane potential with distance: Because current is lost through the “leaky” plasma membrane, the voltage declines with distance from the stimulus (the voltage is decremental ). Consequently, graded potentials are short-distance signals.Membrane potential (mV)Action Potential (AP) Brief reversal of membrane potential with a total amplitude of ~100 mVOccurs in muscle cells and axons of neuronsDoes not decrease in magnitude over distancePrincipal means of long-distance neural communicationActionpotential1234Resting stateDepolarizationRepolarizationHyperpolarizationThe big picture 11234Time (ms)ThresholdMembrane potential (mV)Figure 11.11 (1 of 5)Generation of an Action PotentialResting stateOnly leakage channels for Na+ and K+ are openAll gated Na+ and K+ channels are closedProperties of Gated ChannelsProperties of gated channelsEach Na+ channel has two voltage-sensitive gates Activation gatesClosed at rest; open with depolarization Inactivation gatesOpen at rest; block channel once it is openProperties of Gated ChannelsEach K+ channel has one voltage-sensitive gate Closed at restOpens slowly with depolarization Depolarizing PhaseDepolarizing local currents open voltage-gated Na+ channels Na+ influx causes more depolarizationAt threshold (–55 to –50 mV) positive feedback leads to opening of all Na+ channels, and a reversal of membrane polarity to +30mV (spike of action potential)Repolarizing PhaseRepolarizing phaseNa+ channel slow inactivation gates closeMembrane permeability to Na+ declines to resting levelsSlow voltage-sensitive K+ gates openK+ exits the cell and internal negativity is restoredHyperpolarizationHyperpolarizationSome K+ channels remain open, allowing excessive K+ efflux This causes after-hyperpolarization of the membrane (undershoot)ActionpotentialTime (ms)11234Na+ permeabilityK+ permeabilityThe AP is caused by permeability changes inthe plasma membrane Membrane potential (mV)Relative membrane permeabilityFigure 11.11 (2 of 5)Role of the Sodium-Potassium PumpRepolarization Restores the resting electrical conditions of the neuronDoes not restore the resting ionic conditionsIonic redistribution back to resting conditions is restored by the thousands of sodium-potassium pumpsPropagation of an Action Potential Na+ influx causes a patch of the axonal membrane to depolarizeLocal currents occurNa+ channels toward the point of origin are inactivated and not affected by the local currentsPropagation of an Action Potential Local currents affect adjacent areas in the forward directionDepolarization opens voltage-gated channels and triggers an APRepolarization wave follows the depolarization wave(Fig. 11.12 shows the propagation process in unmyelinated axons.)Figure 11.12aVoltageat 0 msRecordingelectrode(a) Time = 0 ms. Action potential has not yet reached the recording electrode.Resting potentialPeak of action potentialHyperpolarizationFigure 11.12bVoltageat 2 ms(b) Time = 2 ms. Action potential peak is at the recording electrode.Figure 11.12cVoltageat 4 ms(c) Time = 4 ms. Action potential peak is past the recording electrode. Membrane at the recording electrode is still hyperpolarized.Threshold At threshold:Membrane is depolarized by 15 to 20 mV Na+ permeability increasesNa influx exceeds K+ effluxThe positive feedback cycle beginsThreshold Subthreshold stimulus—weak local depolarization that does not reach thresholdThreshold stimulus—strong enough to push the membrane potential toward and beyond threshold AP is an all-or-none phenomenon—action potentials either happen completely, or not at allCoding for Stimulus IntensityAll action potentials are alike and are independent of stimulus intensityHow does the CNS tell the difference between a weak stimulus and a strong one?Strong stimuli can generate action potentials more often than weaker stimuliThe CNS determines stimulus intensity by the frequency of impulsesFigure 11.13ThresholdActionpotentialsStimulusTime (ms) Absolute Refractory PeriodTime from the opening of the Na+ channels until the resetting of the channels Ensures that each AP is an all-or-none eventEnforces one-way transmission of nerve impulsesFigure 11.14StimulusAbsolute refractoryperiodRelative refractoryperiodTime (ms)Depolarization(Na+ enters)Repolarization(K+ leaves)After-hyperpolarizationRelative Refractory PeriodFollows the absolute refractory periodMost Na+ channels have returned to their resting stateSome K+ channels are still openRepolarization is occurringThreshold for AP generation is elevatedExceptionally strong stimulus may generate an APConduction VelocityConduction velocities of neurons vary widely Effect of axon diameterLarger diameter fibers have less resistance to local current flow and have faster impulse conductionEffect of myelinationContinuous conduction in unmyelinated axons is slower than saltatory conduction in myelinated axonsConduction VelocityEffects of myelinationMyelin sheaths insulate and prevent leakage of chargeSaltatory conduction in myelinated axons is about 30 times fasterVoltage-gated Na+ channels are located at the nodesAPs appear to jump rapidly from node to nodeFigure 11.15Size of voltageVoltage-gatedion channelStimulusMyelinsheathStimulusStimulusNode of RanvierMyelin sheath(a) In a bare plasma membrane (without voltage-gatedchannels), as on a dendrite, voltage decays becausecurrent leaks across the membrane. (b) In an unmyelinated axon, voltage-gated Na+ and K+channels regenerate the action potential at each pointalong the axon, so voltage does not decay. Conduction is slow because movements of ions and of the gatesof channel proteins take time and must occur beforevoltage regeneration occurs. (c) In a myelinated axon, myelin keeps current in axons(voltage doesn’t decay much). APs are generated onlyin the nodes of Ranvier and appear to jump rapidlyfrom node to node. 1 mmMultiple Sclerosis (MS)An autoimmune disease that mainly affects young adultsSymptoms: visual disturbances, weakness, loss of muscular control, speech disturbances, and urinary incontinenceMyelin sheaths in the CNS become nonfunctional sclerosesShunting and short-circuiting of nerve impulses occursImpulse conduction slows and eventually ceasesMultiple Sclerosis: TreatmentSome immune system–modifying drugs, including interferons and Copazone:Hold symptoms at bayReduce complicationsReduce disabilityNerve Fiber ClassificationNerve fibers are classified according to:DiameterDegree of myelinationSpeed of conductionNerve Fiber ClassificationGroup A fibersLarge diameter, myelinated somatic sensory and motor fibersGroup B fibersIntermediate diameter, lightly myelinated ANS fibersGroup C fibersSmallest diameter, unmyelinated ANS fibers