4 Neurophysiology

• passive flux of ions (no ATP)

• dependent on the electrochemical potential of the ion

• rapid changes of the membrane potential

• voltage-gated ion channels

  • sodium channels

  • potassium channels

• ligand-gated ion channels

  • glutamate

  • GABA

• mechano-sensory ion channels

  • complicated

• 2 voltage sensors

• 3 activation states

  • resting (closed but can be activated)

  • activated (open)

  • inactivated (closed and CANNOT be activated)

• Pufferfish: Tetrodotoxin (TTX) irreversible

  —> inhibits action potential firing in nerve and muscle cells

  —> death due to respiratory failure

• Lidocaine: local anesthetic, reversible

  —> binds at the intracellular site of the channel

  —> dissociates from the channel after some time

• Opens upon depolarization (delayed)

• K⁺ → outside: repolarization of the action potential

—> use energy in the form of ATP to transport ions across the membrane against their concentration gradient

• Sodium-potassium pump = Na/K-ATPase: exchanges internal Na+ for external K+

velocity is proportional to the root square of the temperature

Movement of ions (e.g. K+)

the drift velocity is proportional to mobility and applied electric field

= reversal potential

= Nernst potential

—> calculate the equilibrium potential (Eion​) for a single type of ion

—> no net flow of a particular ion X

e.g. ion potential = potassium potential

Em - Ek = △E

-70 mV - (-90 mV) = +20 mV —> K+ outward current

Em - Ek = △E

-100 mV - (-90 mV) = -10 —> K+ inward current

Em - Ek = △E

-90 mV - (-90 mV) = 0 —> no movement

membrane potential -70 mV

• potassium K+

  • -70 mV - (-95 mV) = +25 mV —> K+ outward current

• sodium Na+

  • -70 mV - 65 mV = -135 mV —> Na+ inward current

• chloride Cl-

  • -70 mV - (-90 mV) = +20 mV —> Cl- outward current

—> Kalium und Chlorid wollen raus, Natrium (und Calcium) wollen rein

ergänzend:

= the actual resting membrane potential (Vm​) of a real neuron

= Goldmann-Hodgkin-Katz equation

—> provides the formula for the voltage resulting from multiple ions

—> correctly predicts the observed resting potential of -70 mV

R = ideale Gaskonstante

T = Temperatur (K)

F = Faraday-Konstante = elektrische Ladung pro Mol einfach geladener Ionen (ca. 96.485 Coulomb pro Mol)

bei 37, 5°C = 61,5 mV

e.g. resting potential: 61,5 mV ⋅ log10

[(1⋅5)+(0,04⋅145)+(0,45⋅10)] : [(1⋅140)+(0,04⋅15)+(0,45⋅110)]

= 61,5 mV ⋅ log10 [(15,3): (190,1)] = −67,3 mV

K+ increase on the outside

• less potassium diffuses outward

• ΔC becomes weaker

• the potassium equilibrium potential (reverse potential) increases

• closer to the threshold for an action potential = increasing excitability

• Problem: impaired repolarization

K+ decrease on the outside

• more potassium wants to diffuses outward

• ΔC would become higher

• the potassium equilibrium potential (reverse potential) should become more negative and should be more far away from the threshold for an action potential = decreasing excitability

  !BUT!: Kir channels are senstive to low K+ and close Kir channels so K+ cannot get out

  —> Na+ influx increases

  —> increasing excitability!

• stimulus- or transmitter-gated channels open, allowing sodium to flow in

• (PK gets small, PNa increases)

• threshold -55 mV —> voltage-gated sodium channels open abruptly, triggering the “all-or-nothing” response of the action potential

• (PK increases, PNa gets small) —>

• voltage-gated sodium channels get inactivated, voltage-gated potassium channels open

• absolute and relative refractory period

• (Pk high, PNa low)

• Hyperpolarisation

Absolute refractory period: Immediately after an action potential, it is impossible to trigger another one for approximately 1 ms because the sodium channels are inactivated

—> Absolute = AP impossible

Relative refractory period: During the undershoot, the membrane is hyperpolarized, which is why a stronger depolarizing current is needed to reach the threshold again

—> Relative = AP possible, but only with a stronger stimulus

inactivated (closed) —> resting (closed) = ready to be activated again

The faster the voltage-gated sodium channels are regenerated, the faster ends the refractory period —> new AP possible

—> can continously be generated

refractory period determines the direction of action potential propagation

large diameter —> low resistance —> length constant of

its membrane longer —> AP conduction faster

—> Electrical insulation of axons by myelin sheaths

• Spatial Summation

  = adding together of EPSPs (and IPSPs) generated simultaneously at many different synapses on a single dendrite.

• Temporal Summation

  = adding together of EPSPs (and IPSPs) generated at the same synapse if they occur in rapid succession, within about 1–15 msec of one

• Reaching Threshold:

  • 1 single synapse is far too weak to trigger an action potential on its own

  • a neuron must "sum" many small potentials to reach the critical threshold (-55 mV) required to fire

• Neural Computation:

  • perform sophisticated computations rather than acting as simple relay stations

• EPSPs: activating, cause Depolarization

  • Glutamate or ACh

    • AMPA-, Kainat-, Nicotinic ACh receptors (Na+ influx)

    • NMDA (Ca2+ influx)

      • voltage-dependent, magnesium block

• IPSPs: inhibitory, cause Hyperpolarization, called shunting inhibition

  —> taking the potential further away from the firing threshold

  • GABA or Glycine

  • GABA A receptors and Glycine receptors (Cl- influx),

  • [metabotropic GABA B (K+ efflux)]

The neuron essentially performs a continuous "neural computation" by adding and subtracting these inputs.

= field potentials especially in pyramidal cells in the Cortex caused by synaptic electricity produced by dendrites of multiple neurons

• Na+ influx causes negativity in extracellular fluid

• electricity is conducted through dendrite and causes positivity by efflux of the cell in extracellular fluid

  —> when thousands of neurons are activated simultaneously, you can measure a field potential as an EEG-wave

(nobel prize, 1970, german researchers)

= intracellular recording without penetrating the membrane

—> the tip of the electrode is sealed to the membrane (gigaohm seal) instead of penetrating the membrane = more gently and even more precise

MRI (Magnetic Resonance Imaging)

• strong magnetic fields perturb the nuclei of protons in the brain

• radio signal at a specific "resonant frequency” —> protons absorb energy —> emit energy as a detectable radio signal when the pulse is turned off

• ID of tumors, inflammation and lesions (e.g. MS)

PET (Positron Emission Tomography)

• radioactive solution containing positron-emitting isotopes (often attached to glucose) injected into the bloodstream —> emitted positrons interact with electrons to produce photons —> photons tracked by sensors surrounding the head

• active neurons demand more energy —> measurement of neuron activity during specific tasks

SPECT (Single-Photon Emission Computed Tomography)

= Description of organ function at a cellular level

• radioactive substance injected into the bloodstream —> accumulates at target structure e.g. the brain —> sends out single gamma photons —> detected by a camera —> converts it into 3D pictures

fundamental force of nature + critical experimental tool for understanding neurons function

• Electricity = one of the two main factors (alongside diffusion) that drive the movement of ions across the neuronal membrane

• current (I), conductance (g), and potential (V)

  —> I = gV

• use of recording techniques

• electrical synapses —> electric conduction through gap junctions e.g. in the heart without transmission into a chemical signal

• Hebb´sche modification:„Neurons that fire together, wire together“

  • LTP = Long-Term Potentiation

  • long-lasting reinforcement of synaptic transmission between neurons

  • (especially in Hippocampus for learning)

  • synaptic maturation: LTP leads to the incorporation of AMPA receptors, which makes the synapse functional

  • Glutamate release —> AMPA receptor —> Na+ influx —> Mg block resolved from NMDA receptor —> Ca 2+ influx —> cellular mechanisms like increase of AMPA receptors —> cell is more sensitive to Glutamate

<-> LTD: long-term-depression

• long-lasting reduction in synaptic transmission

• weak depolarization

• Magnesium block in the NMDA channel is only partially resolved —> Degradation of AMPA receptors —> weaker synpases