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					A Chord konduktancia -egyenlet The Chord Conductance equation     I= +60  Na+  ∆U  R  g=  1  R  I Cl = ( Em − ECl ) g Cl ≈ 0 I Na = ( Em − E Na ) g Na I K = ( Em − E K ) g K −  −  +  +  0  -70  Em  -90  K+  −  +  +  +  +  Ohm’s law: I = current U = electrical potential R = resistance g = conductance Em = membrane potential EK = equilibrium potential for K ENa = equilibrium potential for Na     In the steady-state (no change in current), the sum of all individual currents through the membrane (i.e, through individual channels) are assumed to be zero. MEANING: NO NET ION CHARGE MOVES ACROSS THE MEMBRANE. (INa+) + (IK+) + (ICl-) + (ICa2+) = 0 If we say that the total conductance gT is the sum of all conductances, then: gT = (gNa+) + (gK+) + (gCl-) + (gCa2+) the above can be solved for the membrane potential.     Relative conductances of the membrane under RESTING conditions gK+ > gNa+ > gCl- > gCa2+ (gCl- and gCa2+ are really small and are usually not considered
in calculations)     The Chord Conductance Equation can be used to calculate Em if the conductances of each ion and their Nernst potentials are known.  Note: This equation predicts that if a particular ion has a high conductance relative to the others, the Em will be near the Nernst potential of that ion. Thus, if a membrane is permeable to only K+ (i.e, gK+ is high and close to gT), then the last 3 terms of the above equation will drop out and Em = EK+.  . But the best approximation is achieved when considering Na+ and K+     +60  Na+  0  -70  Em  -90  K+  A chord konduktancia egyenlet The chord conductance equation     I= +60  Na+  ∆U  g=  R  1  R  I Cl = ( Em − ECl ) g Cl ≈ 0 I Na = ( Em − E Na ) g Na I K = ( Em − E K ) g K −  −  +  +  +  0  +  -90  K+  +  +  +  Em  +  I Na + I K = 0 ( Em − E Na ) g Na = −( Em − E K ) g K g Na gK Em = EK + E Na g K + g Na g K + g Na +  -70  −  +  +  +  +  +  +  +  +  +  100 1 Em = EK + + E Na + 100 + 1 100 + 1 A chord
konduktancia egyenlet The chord conductance equation  +  +     +60  Na+  0  -70  Em  -90  K+  Em = EK+  A chord konduktancia egyenlet Na+ csatorna blokkoló után Chord conductance equation after blockade of Na+ channels     Mechanisms for opening Ion Channels – Ion channels open in response to: • 1: a voltage stimulus – Known as voltage-gated channels • 2: Binding of a ligand – Known as ligand-gated channels • 3: a mechanical stimulus – Known as mechanically gated channels        Control of Ion Channels     Patch Clamp Technique • Lehetővé teszi a membránon keresztüli ionáramok és feszültség, valamint a membránkapacitás mérését. • It allows to measure transmembrane ion currents and voltages as well as changes in membrane capacitance.     Single Channel Recording     Microelectrodes Mikroelektródák     Looking through the microscope Kép a mikroszkóp alatt     Cell-attached Gigaseal     Configurations Konfigurációk     Single Channel Recording Egyes
ioncsatorák vizsgálata     Whole Cell Recording Teljes sejt mérés     AZ AKCIÓS POTENCIÁL KIALAKULÁSA DEVELOPMENT OF ACTION POTENTIAL A SZINAPTIKUS ÁTTEVŐDÉS SYNAPTIC TRANSMISSION Dr. Zsembery Ákos     AKCIÓS POTENCIÁL ACTION POTENTIAL Gyors membrán potenciál változás, melyet a nyugalmi potenciálhoz való visszatérés követ Rapid change in the membrane potential followed by a return to the resting membrane potential     Különböző típusú akcióspotenciálok Different Types of Action Potentials     Az akcióspotenciál fázisai Phases of the Action Potential     Action Potential and Ion Conductivity in Nerve and Skeletal Muscle Cells     Nerve Cells • have a resting potential - set by a constitutively active K+-selective channel (leak K+ channel) • have voltage-gated Na+ channels • have voltage-gated K+ channels     Az idegsejtek akciós potenciáljának kialakulásában a feszültség-függő Na+ és K+ csatornák játszák a főszerepet Voltage-gated Na+
and K+ channels are the major players in generating nerve action potentials     Feszültség-függő Na+ csatornák Voltage-gated Na+ channels • Very few types • Mostly one role – Initiate and propagate action potentials • Structure well known • Three types of conformational state controlled by membrane voltage (resting, activated and inactivated)     Na+ Channel Structure I  II  III  IV Outside  + + +  + + +  + + +  + + + Inside  NH2 COOH     Na+ Channel Conformations αm(Vm)  αh(Vm)  βm(Vm)  βh(Vm)  Resting  Activated  Inactivated  Non-conducting conformation(s)  Conducting conformation  Another non-conducting conformation  (at negative potentials : -90 mV)  (shortly after more depolarized potentials : -90 - +35 mV)  (a while after more depolarized potentials : -90 - +35 mV))     Na+ Channel Gating Na+ Na+ Na+  Na+  Na+ Na+  Na+  Na+  Na+  Na+  Na+  Na+  Na+  Outside  Inside Na+  Na+  Na+ Na+  -15 mV  Na+  -60 mV     Feszültség-függő K+ csatornák Voltage-gated K+
channels • Many types – E.g nerve K+ channels • Many roles – E.g action potential repolarization • Structure is known – Four subunits form homotetramer • Two types of conformational states controlled by membrane potential (closed and open)     Two Conformations α(Vm) β(Vm)  Closed  Open  Non-conducting conformation(s)  Conducting conformation  (at negative potentials)  (at more positive potentials)     Voltage Dependent Gating Outside S1  S2  S3  S4  S5  S6 Inside  HO2C H 2N  + + + + + + LRVIRLVRVFRIFKLSRHS     K+ Channel Gating K+  K+  K+  K+  K+  K+  K+  Outside  Inside K+ K+  K+  -60 mV mV -15  K+ K+  K+  K+  K+  K+  K+  K+     The Action Potential: Na+ and K+ Channels VNa (near +70 mV) Most Na channels open  K channels closed  0 mV Membrane Voltage (mV)  Na channels closed (Not inactivated)  Na channels opening Na channels inactivating K channels opening  K channels closing  VK (near -90 mV)  Na channels un-inactivating Most K channels open Many Na channels
inactivated     The Nerve Action Potential • is a transient reversal of the polarity of the membrane potential • has a rising phase (depolarization) caused by the opening of Na+ channels • has an overshoot that approaches VNa • has a falling phase (repolarization) caused by opening of K+ channels and inactivation of Na+ channels     A TEA és a TTX hatásai az akciós potenciálra  Effects of TEA and TTX on the action potential  TEA: Tetraethylammonium TTX: tetrodotoxin     Refrakter fázisok Refractoriness     A küszöbinger változása a refrakter fázisok alatt Changes in Threshold During Refractory Periods     The Nerve Action Potential • has an absolute refractory period because most Na+ channels are first rapidly opening and then rapidly becoming inactivated • has a relative refractory period because some Na+ channels are inactivated and some K+ channels are open • propagates in one direction along axons through the sequential action of Na+ channels
(“unidirectional”)