CEL. & MOL. NEUROSCIENCES:
PART II MOLECULAR NEUROSCIENCES
1. Introduction
The complex brain: interaction of 8 levels
- We focus on neurons, synapses and molecules
Charging of a cell membrane
- Cell membrane exist of resistor (R) and capacitor (C)
- R = 1/g !! → resistor ad conductance are hardly associated
- The voltage changes are never instantaneous !
- The current mainly charges the capacitor
o The initial current is mainly capacitive and then the capacitive current decrease (2D)
o As the capacitive current decreases and reaches steady state , the current of the resistor increases
o In C there is only resistor current
o BUT in reality steady state doesn’t exist, there is always changes in voltage
- Input resistance: you put a current and measure the steady state voltage change, then you can measure the
resistance → So it is a measurement
1
,Origin of the resting membrane potential
- Resting potential: due to a disequilibrium in K conc in and out the cell
- B= when we stop the current
→ The decay is exponential
- τm= membrane time constant
o Capacitance = constant, R = can change
o For neurons this is ~10-50ms → it takes 50mss to reach 66% decay of the voltage
Relation between current and potential
- I = g * V = linear equation
o Theoretical
o The slope of the line is determined by conductance → Higher conductance→ Steeper line
o Crosses the axis at 0
2
, - I = g (V-Er) = linear equation
o Ion Channels (conducting membrane current) and synaptic channels (activated by neurotransmitters)
are not dependent on the absolute voltage (V) BUT are dependent on the difference between the
membrane potential and the reversal potential (V-Er)
o Crosses the x-axis at reversal potential → the current changes sign: negative → positive
o Conductance = constant
- Non-linear conductance = voltage gated
o Channels undergo conformational changes depending on voltages
→ Voltage dependent channel opening
o At some voltages → 0 current , at some voltages→ max current
o The transition between the voltages is gradually
o Conductance: changes
- When you cross reversal potential the current becomes positive, ions are now leaving the cell
o This is only possible if there are enough ions = problem for Ca
Note: in practice channels can’t cross their own reversal potential, because there is almost no current at the
reversal potential
Action potential generation
Voltage clamp to measure ionic currents
3
, - The original H&H method is almost not used anymore
- NOW: left: high-tech approach; 2 micro electrodes
o 1 measures the voltage and measures what current you need to inject to stay at the clamp/ desired
level
o The second electrode gives the additional current
o This current is the opposite of the intrinsic current that the neuron is producing
▪ That is why Inward → hyperpolarizing – downward → depolarizing
- BUT if you go in small paths (axon) it doesn’t fit, 2 electrodes are too big
- Right: Patch clamp = solution
o You measure the voltage and inject the current with the same electrodes
o But not perfect
Limitations of H&H model
1) Single channel gating is much more complex than compound currents they measured
2) Inactivation is NOT purely voltage dependent
3) Not all currents are Ohmic
1) Single channel gating is much more complex than compound currents they measured
→ Na inactivates, K doesn’t inactivate, it reaches steady state
→ There is more variability in single channel currents
4
PART II MOLECULAR NEUROSCIENCES
1. Introduction
The complex brain: interaction of 8 levels
- We focus on neurons, synapses and molecules
Charging of a cell membrane
- Cell membrane exist of resistor (R) and capacitor (C)
- R = 1/g !! → resistor ad conductance are hardly associated
- The voltage changes are never instantaneous !
- The current mainly charges the capacitor
o The initial current is mainly capacitive and then the capacitive current decrease (2D)
o As the capacitive current decreases and reaches steady state , the current of the resistor increases
o In C there is only resistor current
o BUT in reality steady state doesn’t exist, there is always changes in voltage
- Input resistance: you put a current and measure the steady state voltage change, then you can measure the
resistance → So it is a measurement
1
,Origin of the resting membrane potential
- Resting potential: due to a disequilibrium in K conc in and out the cell
- B= when we stop the current
→ The decay is exponential
- τm= membrane time constant
o Capacitance = constant, R = can change
o For neurons this is ~10-50ms → it takes 50mss to reach 66% decay of the voltage
Relation between current and potential
- I = g * V = linear equation
o Theoretical
o The slope of the line is determined by conductance → Higher conductance→ Steeper line
o Crosses the axis at 0
2
, - I = g (V-Er) = linear equation
o Ion Channels (conducting membrane current) and synaptic channels (activated by neurotransmitters)
are not dependent on the absolute voltage (V) BUT are dependent on the difference between the
membrane potential and the reversal potential (V-Er)
o Crosses the x-axis at reversal potential → the current changes sign: negative → positive
o Conductance = constant
- Non-linear conductance = voltage gated
o Channels undergo conformational changes depending on voltages
→ Voltage dependent channel opening
o At some voltages → 0 current , at some voltages→ max current
o The transition between the voltages is gradually
o Conductance: changes
- When you cross reversal potential the current becomes positive, ions are now leaving the cell
o This is only possible if there are enough ions = problem for Ca
Note: in practice channels can’t cross their own reversal potential, because there is almost no current at the
reversal potential
Action potential generation
Voltage clamp to measure ionic currents
3
, - The original H&H method is almost not used anymore
- NOW: left: high-tech approach; 2 micro electrodes
o 1 measures the voltage and measures what current you need to inject to stay at the clamp/ desired
level
o The second electrode gives the additional current
o This current is the opposite of the intrinsic current that the neuron is producing
▪ That is why Inward → hyperpolarizing – downward → depolarizing
- BUT if you go in small paths (axon) it doesn’t fit, 2 electrodes are too big
- Right: Patch clamp = solution
o You measure the voltage and inject the current with the same electrodes
o But not perfect
Limitations of H&H model
1) Single channel gating is much more complex than compound currents they measured
2) Inactivation is NOT purely voltage dependent
3) Not all currents are Ohmic
1) Single channel gating is much more complex than compound currents they measured
→ Na inactivates, K doesn’t inactivate, it reaches steady state
→ There is more variability in single channel currents
4
