Biofisika Neuron 2006

BIOFISIKA NEURONBIOFISIKA NEURON(Biophysics of Neuron)(Biophysics of Neuron)

H Aqsa SjuhadaH Aqsa SjuhadaBuilding DR-GBuilding DR-G

Dept of Physiology, Airlangga UniversityDept of Physiology, Airlangga UniversityTel. (031) 71200 999Tel. (031) 71200 999

E-mail. [email protected]. [email protected]

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CHAPTER 1CHAPTER 1

Transmembrane regulationTransmembrane regulation Biology of the Neuron Biology of the Neuron

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BODY LIQUIDBODY LIQUID Total : 60%Total : 60% Intracellular: 40%Intracellular: 40% Extracell: 20% (kecuali cair Extracell: 20% (kecuali cair

serebrospinal, cairan sendi, cairan serebrospinal, cairan sendi, cairan saliva)saliva)

- cairan interstitial 15%- cairan interstitial 15%- cairan plasma 5%- cairan plasma 5%- cairan sel darah- cairan sel darah- cairan intra vaskuler- cairan intra vaskuler

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TRANSPORT BAHANTRANSPORT BAHAN

ACTIVE TRANSPORTACTIVE TRANSPORT1. primary1. primary2. secondary 2. secondary

- bulk transport- bulk transport- exocytosis- exocytosis- endocytosis- endocytosis

- phagocytosis- phagocytosis- pinocytosis- pinocytosis

PASSIVE TRANSPORTPASSIVE TRANSPORT- osmosisosmosis- diffusiondiffusion- filtration- filtration-solvent dragsolvent drag

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ACTIVE ACTIVE TRANSPORTTRANSPORT

PASSIVE PASSIVE TRANSPORTTRANSPORT

CELLULAR CELLULAR ENERGYENERGY

requiredrequired not required, not required, only kinetic only kinetic energyenergy

PROCESSPROCESS physiology - physiology - biologybiology

physicsphysics

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DIFFUSIONDIFFUSION

Particle movementParticle movement Simple diffusion : Simple diffusion : O2, CO2, alcoholO2, CO2, alcohol Facilitated diffusion : Facilitated diffusion : glucose, amine acidglucose, amine acid

OSMOSISOSMOSIS Liquid movementLiquid movement Hypotonic -Hypotonic - Hypertonic Hypertonic

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MACAMMACAM GERAKAN GERAKAN DARIDARI

ARAH ARAH GERAKAGERAKANN

PLASMA PLASMA MEMBRAMEMBRANN

CARRIER CARRIER SYSTEMSYSTEM

ENERGY ENERGY CELLULACELLULARR

OsmosOsmosisis

SolventSolvent C↓→C↑ C↓→C↑ SPSP TidakTidak TidakTidak

DiffusiDiffusi SolutSolut C↑→C↓ C↑→C↓ +/-+/- TidakTidak TidakTidak

Active Active TranspTransp

SolutSolut C↓→C↑ C↓→C↑ SPSP AdaAda AdaAda

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SEL EKSITABELSEL EKSITABEL

Sel yg mampu menimbulkan / Sel yg mampu menimbulkan / menjalankan impuls elektrokimia menjalankan impuls elektrokimia sepanjang membran plasmanya.sepanjang membran plasmanya.

→ → Sel saraf, sel otot, sel kelenjarSel saraf, sel otot, sel kelenjar

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MEMBRAN PLASMAMEMBRAN PLASMASTRUKTUR DAN KOMPOSISI MEMBRAN PLASMASTRUKTUR DAN KOMPOSISI MEMBRAN PLASMA Lemak → dynamic mozaic design / lipid bilayer 42%Lemak → dynamic mozaic design / lipid bilayer 42% Protein 55%Protein 55% Karbohidrat 3%Karbohidrat 3%

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SIFATSIFAT - Elastis tipis, ketebalan 6-10nmElastis tipis, ketebalan 6-10nmFUNGSIFUNGSI- Physical isolationPhysical isolation- Regulation of exchange with the Regulation of exchange with the

environment --- nutrition, ionenvironment --- nutrition, ion- Sensitivity --- receptor functionSensitivity --- receptor function- Structural supportStructural supportJENISJENIS- ImpermeableImpermeable- Semi permeableSemi permeable- Selective permeableSelective permeable

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PROTEINPROTEIN

Sebagian besar glicoproteinSebagian besar glicoprotein

Protein integral / protein perifer, fungsinya:Protein integral / protein perifer, fungsinya: membatasi pergerakan membran plasmamembatasi pergerakan membran plasma sebagai channelsebagai channel carrier systemcarrier system enzymeenzyme receptorreceptor

Karbohidrat; berada di luar berikatan dg Karbohidrat; berada di luar berikatan dg glicoprotein maupun lipid bilayer, fungsi: glicoprotein maupun lipid bilayer, fungsi: sebagai indikator sel.sebagai indikator sel.

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NEURONEURONN

= Sel saraf= Sel saraf

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DentritesDentrites Cell BodyCell Body AxonAxon TerminalTerminal

A Typical Neuron OverviewA Typical Neuron Overview

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Diverse Neuron Forms and FunctionsDiverse Neuron Forms and Functions

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Cell body site of energy generation and Cell body site of energy generation and synthesissynthesis

Axonal transportAxonal transport Vesicles –Vesicles –

Fast axonal transport to terminalFast axonal transport to terminal Retrograde to cell bodyRetrograde to cell body

Electrical depolarizationsElectrical depolarizations

Metabolism and Synthesis in a Metabolism and Synthesis in a NeuronNeuron

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Metabolism and Synthesis in a Metabolism and Synthesis in a NeuronNeuron

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Support neuron bodies, form myelin sheathsSupport neuron bodies, form myelin sheaths Barriers between compartmentsBarriers between compartments Scavenger/defense & metabolic assistanceScavenger/defense & metabolic assistance

Glial Cell FunctionsGlial Cell Functions

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Glial Cell FunctionsGlial Cell Functions

Figure 8-5: Glial cells and their functions

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Electrical Signals: Electrical Signals: Ionic Concentrations and Ionic Concentrations and

PotentialsPotentials Nernst & GHK Equations predict Nernst & GHK Equations predict

Membrane potentialMembrane potential Cell concentration gradientsCell concentration gradients

[Na[Na++, Cl, Cl-- & Ca & Ca2+2+] higher in ECF] higher in ECF [K[K++] higher ICF] higher ICF

Depolarization causes electrical signalDepolarization causes electrical signal Gated channels control permeabilityGated channels control permeability

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Electrical Signals: Electrical Signals: Ionic Concentrations and Ionic Concentrations and

PotentialsPotentials

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CHAPTER 2CHAPTER 2

Membrane PotentialMembrane Potential Action PotentialAction Potential

Synaptic Transmission Synaptic Transmission

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Basic ConceptsBasic Concepts

VoltVolt

A charge difference between two A charge difference between two points in spacepoints in space

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Basic ConceptsBasic Concepts

Ions – charged particlesIons – charged particles

Anions – Negatively charged Anions – Negatively charged particlesparticles

Cations – Positively charged Cations – Positively charged particlesparticles

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Basic ConceptsBasic ConceptsForces that determine ionic Forces that determine ionic

movementmovement Electrostatic forcesElectrostatic forces

Opposite charges attract, Identical charges Opposite charges attract, Identical charges repelrepel

Concentration forcesConcentration forces Diffusion – movement of ions through Diffusion – movement of ions through

semipermeable membranesemipermeable membrane Osmosis – movement of water from region of Osmosis – movement of water from region of

high concentration to lowhigh concentration to low Hydrostatic ForcesHydrostatic Forces

Gravity forces upon osmosisGravity forces upon osmosisThe combination of these forces leads to The combination of these forces leads to

dynamic equilibrium in the cellular dynamic equilibrium in the cellular environmentenvironment

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Basic ConceptsBasic ConceptsThe selective The selective

permeability of membranespermeability of membranes

Neuronal membranes Neuronal membranes

Hydrophobic lipid bilayerHydrophobic lipid bilayer Two fatty layers separated by proteinTwo fatty layers separated by protein

Gated ion channelsGated ion channels

Nongated ion channelsNongated ion channels

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ForcesForcesthat determine the movement of that determine the movement of

ionsions DiffusionDiffusion

OsmosisOsmosis

Electrostatic ForcesElectrostatic Forces

Hydrostatic ForcesHydrostatic Forces

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Selective Permeability of Selective Permeability of MembranesMembranes

Some ions permitted to cross more Some ions permitted to cross more easily than otherseasily than others

Neuronal membranes contain ion Neuronal membranes contain ion channelschannels Protein tubes that span the membraneProtein tubes that span the membrane Some stay open all the time (nongated)Some stay open all the time (nongated) Some open on the occasion of an action Some open on the occasion of an action

potential, causing a change in the potential, causing a change in the permeability of the membrane (gated)permeability of the membrane (gated)

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Membrane Resting Membrane Resting PotentialPotential The electrochemical state of the The electrochemical state of the

neuron at restneuron at rest

Cell’s ability to fire an action Cell’s ability to fire an action potential is due to the cell’s ability potential is due to the cell’s ability to maintain the cellular resting to maintain the cellular resting potential at approximately potential at approximately

– –70 mV (-.07 volt)70 mV (-.07 volt)

The basic signaling properties of The basic signaling properties of neurons are determined by neurons are determined by changes in the resting potentialchanges in the resting potential

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Membrane Resting Membrane Resting PotentialPotential

Every neuron has a separation of electrical charge Every neuron has a separation of electrical charge across its cell membrane.across its cell membrane.

The membrane potential results from a separation The membrane potential results from a separation of positive and negative charges across the cell of positive and negative charges across the cell membrane.membrane.

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Membrane Resting Membrane Resting PotentialPotential

excess of positive excess of positive charges outside and charges outside and negative charges negative charges inside the membrane inside the membrane

maintained because maintained because the lipid bilayer acts the lipid bilayer acts as a barrier to the as a barrier to the diffusion of ions diffusion of ions

• gives rise to an electrical potential difference, which ranges from about 60 to 70 mV.

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Membrane Resting PotentialMembrane Resting Potential

The charge The charge separation across the separation across the membrane, and membrane, and therefore the resting therefore the resting membrane potential, membrane potential, is disturbed whenever is disturbed whenever there is a net flux of there is a net flux of ions into or out of the ions into or out of the cellcell. .

• A reduction of the charge separation is called depolarization;

• An increase in charge separation is called hyperpolarization

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Besar RMP –70 mV Besar RMP –70 mV Artinya ?Artinya ? Potensial elektriks di dalam membran sel Potensial elektriks di dalam membran sel

lebih negatif dibandingkan di luar lebih negatif dibandingkan di luar membran sel sebesar 70mVmembran sel sebesar 70mV

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POTENSIAL MEMBRANPOTENSIAL MEMBRAN Perbedaan muatan listrik di luar dan Perbedaan muatan listrik di luar dan

di dalam membran seldi dalam membran selRMPRMP =Resting Membran Potential=Resting Membran Potential =Potensial Membran Istirahat=Potensial Membran Istirahat Berbedaan muatan listrik di luar dan Berbedaan muatan listrik di luar dan

di dalam membran sel dalam keadaan di dalam membran sel dalam keadaan tidak ada aktivitas elektris.tidak ada aktivitas elektris.

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Ion ChannelsIon Channels

A class of integral proteins that span the A class of integral proteins that span the cell membranecell membrane

Permit Transient current flowPermit Transient current flow Facilitate Depolarization, Facilitate Depolarization,

HyperpolarizationHyperpolarization

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Ion ChannelsIon Channels

Two Types of Ion ChannelsTwo Types of Ion Channels

1. Gated1. Gated

2. Non-Gated2. Non-Gated

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Ion ChannelsIon Channels Recognize and select among specific Recognize and select among specific

ionsions

The distribution of ionic species The distribution of ionic species across the membrane depends on the across the membrane depends on the particular distribution of ion channels particular distribution of ion channels in the cell membrane.in the cell membrane.

Ionic species are not distributed Ionic species are not distributed equally on the two sides of a nerve equally on the two sides of a nerve membranemembrane

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Resting Membrane Resting Membrane PotentialPotential

Na+ and Cl- are more Na+ and Cl- are more concentrated outside the cell concentrated outside the cell

K+ and organic anions (organic K+ and organic anions (organic acids and proteins) are more acids and proteins) are more concentrated inside. The overall concentrated inside. The overall effect of this ionic distribution is effect of this ionic distribution is the resting potentialthe resting potential

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Two forces acting on a given ionic Two forces acting on a given ionic speciesspecies

Chemical forces tend to drive ions down Chemical forces tend to drive ions down their concentration gradientstheir concentration gradients

• Chloride ions, concentrated outside the cell tend to move inward down their concentration gradient through nongated chloride channels

• But the relative excess of negative charge inside the membrane tend to push chloride ions back out of the cell

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Resting Membrane PotentialResting Membrane Potential

The same mechanisms operate on The same mechanisms operate on potassium…potassium…

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But what about sodium?But what about sodium? Electrostatic and Chemical forces act Electrostatic and Chemical forces act

together on Na ions to drive them into the together on Na ions to drive them into the cellcell

Na is more concentrated outside than inside and therefore tends to flow into the cell down its concentration gradient

Na is driven into the cell by the electrical potential difference across the membrane.

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this process cannot be allowed to continue unopposedthis process cannot be allowed to continue unopposed Otherwise, the K pool would be depleted, intracellular Otherwise, the K pool would be depleted, intracellular

Na would increase, and the ionic gradients would Na would increase, and the ionic gradients would gradually run down, reducing the resting membrane gradually run down, reducing the resting membrane potential. potential.

•Electrostatic and Chemical forces act together on Na ions to drive them into the cell

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The Sodium-Potassium The Sodium-Potassium PumpPump

Dissipation of ionic gradients is Dissipation of ionic gradients is ultimately prevented by Na-K ultimately prevented by Na-K pumpspumps

extrudes Na from the cell while taking in K

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The Sodium-Potassium The Sodium-Potassium PumpPump

Because the pump moves Na and K against their Because the pump moves Na and K against their net electrochemical gradients, energy is required net electrochemical gradients, energy is required to drive these actively transported fluxes. to drive these actively transported fluxes.

Chloride pumps also that actively transport Chloride pumps also that actively transport chloride ions toward the outside assure that the chloride ions toward the outside assure that the extra- to intracellular Cl concentration is greater extra- to intracellular Cl concentration is greater than what would result from passive diffusion than what would result from passive diffusion alone. alone.

The energy necessary for this process is obtained from the hydrolysis of ATP (an energy carrying molecule)

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RANGSANGANRANGSANGAN

AdekuatAdekuat Tidak adekuatTidak adekuat

Mencapai thresholdMencapai threshold Tidak mencapai Tidak mencapai thresholdthreshold

POTENSIAL AKSIPOTENSIAL AKSI LOCAL LOCAL POTENTIALPOTENTIAL

Dirambatkan ke segala arahDirambatkan ke segala arah Tidak Tidak dirambatkandirambatkan

Hukum ALL OR NONEHukum ALL OR NONE SumasiSumasi

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Action PotentialAction Potential

The basic unit of conduction in The basic unit of conduction in the nervous systemthe nervous system

This change or “overshoot” is This change or “overshoot” is called the “Action Potential” called the “Action Potential”

Characteristic of axonsCharacteristic of axons Non-decremental conduction – Non-decremental conduction –

““all-or-none law”all-or-none law”

TUGAS : BUAT DEFINISI SENDIRITUGAS : BUAT DEFINISI SENDIRI

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Action Potential SequenceAction Potential Sequence

Involves the action of voltage-gated channelsInvolves the action of voltage-gated channels Exchanges of ions in and out of the cellExchanges of ions in and out of the cell

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Action Potential Stages: Action Potential Stages: OverviewOverview

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ANIMASI ACTION POTENTIALANIMASI ACTION POTENTIAL

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Action Action Potential Potential

SequenceSequence

Saluran Na+ terbuka, terjadilah Saluran Na+ terbuka, terjadilah fast natrium influx, depolarisasi.fast natrium influx, depolarisasi.

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SequenceSequence

Pada keadaan +40 mV, saluran Na+ menutup, tetapi Pada keadaan +40 mV, saluran Na+ menutup, tetapi saluran K+ sekarang terbuka, menyebabkan pengeluaran saluran K+ sekarang terbuka, menyebabkan pengeluaran ion K+ (gradien konsentrasi), menyebabkan penurunan ion K+ (gradien konsentrasi), menyebabkan penurunan gradien elektris.gradien elektris.

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SequenceSequence

Saluran K+ menutup, Saluran K+ menutup, terjadilah akumulasi ion K+ di terjadilah akumulasi ion K+ di ekstrasel. Hal ini ekstrasel. Hal ini menyebabkan depolarisasi, menyebabkan depolarisasi, sedemikian rupa sehingga sedemikian rupa sehingga terjadi undershoot pada akhir terjadi undershoot pada akhir action potentialaction potential

Equilibrium membran potential dikembalikan

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SequenceSequence

Na+-K+ pump (pompa Na+-K+) berfungsi Na+-K+ pump (pompa Na+-K+) berfungsi mengembalikan keadaan serupa, yaitu RMP.mengembalikan keadaan serupa, yaitu RMP.

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Membrane & Channel Changes Membrane & Channel Changes during an Action Potentialduring an Action Potential

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Refractory PeriodRefractory Period

Two typesTwo types AbsoluteAbsolute

When Na+ channels close, at peak When Na+ channels close, at peak of AP, they do not reopen for a timeof AP, they do not reopen for a time

RelativeRelative Membrane hyperpolarizedMembrane hyperpolarized Some Na+ channels still refractorySome Na+ channels still refractory

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Propagation of the Action Propagation of the Action PotentialPotential

Action Potential spreads down Action Potential spreads down the axon in a chain reaction the axon in a chain reaction

Unidirectional Unidirectional it does not spread into the cell body it does not spread into the cell body

and dendrite due to absence of and dendrite due to absence of voltage-gated channels therevoltage-gated channels there

Refraction prevents spread back Refraction prevents spread back across axonacross axon

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Speed of propagation varies with Speed of propagation varies with the axon diameterthe axon diameter

Faster with larger axonsFaster with larger axons In large axons of mammalsIn large axons of mammals

5m/second 25m/second 2m axonsm axons 20m/second in 2020m/second in 20m axonsm axons

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Speed of propagation also Speed of propagation also assisted by the myelin sheathassisted by the myelin sheath Provides resistance to APProvides resistance to AP

Regular gaps in the myelin Regular gaps in the myelin sheath (1mm intervals)sheath (1mm intervals) ““Nodes of Ranvier”Nodes of Ranvier” Increase conduction speed up to 15 Increase conduction speed up to 15

timestimes

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Biofisika Neuron 2006

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