Ionic basis of the resting membrane potential. Foundations in Neuroscience I, Oct

Transcription

1 Ionic basis of the resting membrane potential Foundations in Neuroscience I, Oct

2 The next 4 lectures... - The resting membrane potential (today) - The action potential - The neural mechanisms behind them (voltage gated ion channels) - Neurotransmitter release

3 Resting potential and action potential: simple view -

4 Big ideas: Resting membrane potential - Ion transport across the membrane The electrochemical gradient Equilibrium potential for Na+, K+ and ClNernst and GHK equations Passive membrane properties Electrical circuit model of the membrane Simulations!

5 Resting membrane potential

6 Review: Cell membrane Credit: Mariana Ruiz Villarreal

7 Review: Transport across the cell membrane

8 Review: Transport across the cell membrane

9 Review: Transport across the cell membrane

10 Movie?

11 Electrochemical gradient

12 Electrochemical gradient: reaching equilibrium Positive ions flow down concentration gradient, from out to in Cell interior becomes electropositive Net ion flow stops when there is enough positive charge inside to prevent more positive ions from coming in Electrical potential at which net ion flow is zero -> Equilibrium potential Depends on concentration of the ions in and out of the cell

13 Major ions that determine resting potential: Na+, K+, and ClIon Extracellular Intracellular K+ 4 Na Cl- 5 Na+/K+ pump

14 Major ions that determine resting potential: Na+, K+, and ClIon Extracellular Intracellular Equilibrium potential K+ 4 <0 Na >0 Cl- 5 <0 Na+/K+ pump

15 Resting membrane potential

16 Major ions that determine resting potential: Na+, K+, and ClIon Extracellular Intracellular Membrane permeability K+ 4 high Na low Cl- 5 low Na+/K+ pump

17 Super key point: The membrane potential is dominated by the ion with the largest permeability Ion Extracel. Intracellular Membrane permeability K+ 4 high Na low Cl- 5 low

18 Nernst Equation and equilibrium potentials Ion Extracellular Intracellular Membrane permeability K+ 4 high <0 Na low >0 Cl- 5 low <0 Equilibrium potential

19 Nernst Equation and equilibrium potentials Ion Extracellular Intracellular Membrane permeability K+ 4 high Equilibrium potential <0 [K+]out : ion concentration outside the cell [K+]in : ion concentration inside the cell z: charge of the ion (signed) T: Temperature in Kelvin R: constant (universal gas constant 8.3 Joules/molK F: constant (Faraday constant 9.6 x104 coulombs/mol)

20 Nernst Equation and equilibrium potentials Ion Extracellular Intracellular Membrane permeability K+ 4 high Equilibrium potential <0 [K+]out : ion concentration outside the cell [K+]in : ion concentration inside the cell z: charge of the ion (signed) T: Temperature in Kelvin R: constant (universal gas constant 8.3 Joules/molK F: constant (Faraday constant 9.6 x104 coulombs/mol)

21 Nernst Equation and equilibrium potentials Ion Extracellular Intracellular Membrane permeability K+ 4 high Equilibrium potential <0 [K+]out : ion concentration outside the cell [K+]in : ion concentration inside the cell z: charge of the ion (signed) T: Temperature in Kelvin R: constant (universal gas constant 8.3 Joules/molK F: constant (Faraday constant 9.6 x104 coulombs/mol)

22 Nernst Equation and equilibrium potentials Ion Extracellular Intracellular Membrane permeability K+ 4 high Equilibrium potential <0 [K+]out : ion concentration outside the cell [K+]in : ion concentration inside the cell z: charge of the ion (signed) T: Temperature in Kelvin R: constant (universal gas constant 8.3 Joules/molK F: constant (Faraday constant 9.6 x104 coulombs/mol)

23 Nernst Equation and equilibrium potentials for: Na+ and ClIon Extracellular Intracellular Membrane permeability K+ 4 high -85 Na low >0 Cl- 5 low <0 Equilibrium potential

24 Equilibrium potentials for K+, Na+, and Cl- Ion Extracellular Intracellular Membrane permeability K+ 4 high -85mV Na low 58mV Cl- 5 low -79mV Equilibrium potential

25 Equilibrium potentials for K+, Na+, and Cl- Ion Extracellular Intracellular Membrane permeability K+ 4 high -85mV Na low 58mV Cl- 5 low -79mV Equilibrium potential

26 Bringing it all together: the GHK Equation Ion Extracellular Intracellular Membrane permeability K+ 4 high -85mV Na low 58mV Cl- 5 low -79 Equilibrium potential Goldman-Hodgkin-Katz (GHK) equation for K+, Na+ and Cl-

27 GHK Example: membrane only permeable to Na+ Ion Extracellular Intracellular Membrane permeability K mV Na >0 58mV Cl mV Equilibrium potential Goldman-Hodgkin-Katz (GHK) equation for K+, Na+ and Cl- Vm = ENa = 58mv

28 Bringing it all together: the GHK Equation Ion Extracellular Intracellular Membrane permeability K+ 4 high -85mV Na low 58mV Cl- 5 low -79mV Equilibrium potential Goldman-Hodgkin-Katz (GHK) equation for K+, Na+ and Cl- Vm E K = -75mV

29 Driving force and Na+/K+ pumps Ion Extracellular Intracellular Membrane permeability K+ 4 high -85mV Na low 58mV Cl- 5 low -79mV Equilibrium potential Difference between Vm and Equilibrium potential: Driving force Ek < -75mV ENa > -75mV ECl -75mV K leaks out of the cell Na leaks into the cell Little net Cl- flow Vm E K = -75mV

30 Somewhere in here would be good to explain that ion concentrations remain stable, that ionic imbalance is extremely tiny in the molar sense, but that it has big effects on electrical potential.

31 Pause: Everything cool?

32 Electrical circuit model for a neuron

33 RC circuits: Resistors Ohms law Serial resistance adds linearly V = IR R = R 1 + R2 V = I/g 1/g = 1/g1 + 1/g2 I = gv Serial conductance adds inversely Parallel resistance adds inversely 1/R = 1/R1 + 1/R2 g = g1 + g2 Parallel conductance adds linearly

34 RC circuits: Capacitors

35 Electrical circuit model for a neuron Capacitor: Lipid membrane, charges accumulate on either side Resistor (conductance): ion-specific channels e.g. K+ leak channels Battery: Equilibrium potential -- i.e. the electrochemical gradient for each ion that drives ion flow across the membrane.

36 A neuron circuit model Same Vm regardless of the path through the circuit Vm Circuit equivalent of GHK equation

37 Explain current clamp recordings here

38 Do movie here?

39 Passive properties of neurons and axons Voltage changes slowly over time due to capacitance of cell membrane

40 Passive properties of neurons and axons Time constant for charging membrane Higher time constant slower charging time, slower signal propagation, more temporal integration Lower time constant faster charging time, faster signal propagation, less temporal integration Membrane time constant RmCm... due to capacitance of cell membrane

41 Passive properties of neurons and axons Voltage decays over distance...

42 Passive properties of neurons and axons Voltage decays over distance... Im Im Im Im... due to leaky membrane current

43 Cable properties Length constant for signal spread Voltage along axon at distance (x) from current source Where voltage is maximal (V0) Longer length constant longer propagation of voltage Shorter length constant shorter propagation of voltage Im Im Im Im

44 Cable properties recap Time constant for charging capacitor Length constant for current spread RmCm Higher time constant slower charging time, slower signal propagation, more temporal integration Lower time constant faster charging time, faster signal propagation, less temporal integration Longer length constant longer propagation of voltage Shorter length constant shorter propagation of voltage

45 Summary: electrochemical gradient Ion Extracellular Intracellular Membrane permeability K+ 4 high -85mV Na low 58mV Cl- 5 low -79mV Equilibrium potential

46 Summary: Nernst and GHK Ion Extracellular Intracellular Membrane permeability K+ 4 high -85mV Na low 58mV Cl- 5 low -79mV Equilibrium potential

47 Summary: RC circuit model of the neuron Same Vm regardless of the path through the circuit Vm Circuit equivalent of GHK equation

48 Summary: passive properties of neurons and axons Voltage decays over distance... RmCm Time constant Length constant

49 Simulations! - Start SimCC program (current clamp mode) File Open to load file Start with StepResistance.cc5 Hit Control-Y to run the simulation Top trace is voltage Bottom trace is injected current Parameters menu controls the simulation Menus on upper right control the display