Signal Transmission (Electrophysiology)

Question 1

Nernst equation

Answer 1

Relates the effective concentrations of cell reaction components to the standard potential

Question 2

Equilibrium potential/concentrations of ions

Answer 2

K+: Outside 5 mM, inside 100 (1:20) → -80mV
Na+: Outside 150 mM, inside 15 (10:1) → 62mV
Ca2+: Outside 2mM, inside 0.0002 (10.000:1) → 123 mV
Cl-: Outside 150 mM, inside 13 (11.5:1) → -65 mV

Question 3

Goldmann-Hodgkin-Katz equation

Answer 3

Calculate the membrane potential → Put together the Nernst equation of all the involved ions

Question 4

Conductance

Answer 4

Sum of all ions passing the neuron at a specific time

Question 5

Na+/K+ ATPase

Answer 5

ATP dependent transport of 3 Na+ outside & 2 K+ inside

Binding of ATP + 3 Na+ → ATP hydrolization → Phosphorylation at aspartate → Release ADP → Conformational change → Na+ released ec → Binding of 2 K+ → >Induction of dephosphorylation → K+ ic released

Question 6

Na+/K+-ATPase involvment in diseases

Answer 6

Alpha1: Omnipresent → Involved in hypertension
Alpha2: Muscle & brain → Easier depolarization in FHM
Alpha3: Brain → Involved in AHC, ROP & CAPOS

Question 7

Ca2+-ATPase

Answer 7

Ca2+ transport independend of other ions
3 types: SERCA, SPCA & AMCA
Ca2+ binding → Mg-ATP binding & bend in TM region → ATP cleavage → Increased Bend → Release of Ca2+ & binding of two protons → Unstable → Bend back, release of proton & Mg

Question 8

Cl- Transport

Answer 8

NKCC1: Neonatal, Na+ dependent (1Na+ : 1K+ : 2 Cl-) → Lots of Cl- inside = Inhibitory
KCC2: Cl- pumped to the outside (1K+ : 1 Cl- = Na+ independent)

Question 9

Patch-Clamp

Answer 9

Study ionic currents → Micropipette with electrolyte solution
Cell-attached: Pipette sealed on membrane → Record currents of a few contained ion channels
Whole cell recording: Rupture cell membrane → Means to administer & study drugs
Inside-out-patch: Vescile formation → Single channel analysis
Outside-out-patch: Bulb of membrane blebs out of cell → Single channel analysis

Question 10

Action Potential

Answer 10

= Short-lasting marked change in the membrane potential → Generated at the axon hillock

Question 11

Summation of the Action Potential

Answer 11

Temporal summation: Duration of the postsynaptic potential longer than interval between APs → Repeated inputs
Spatial summation: Simultaneous inputs from multiple presynaptic cells

Question 12

Translation of the Action Potential

Answer 12

Stimulus → Transduction → Receptor potential → Transformation → AP
Ion channels necessary to translate & transmit the AP

Question 13

Stages of the Action Potential

Answer 13

Initiation: Voltage increase (From -70mV to -50 mV)
Spread: Threshold potential exceeded → Depolarization → Opening of NaV → Na+ influx
Repolarization: At around 62 mV, NaV close, KV open → Efflux of K+ → Back to resting potential
Hyperpolarization: KV close slowly → Membrane potential below resting potential

Question 14

Propagation of the Action Potential

Answer 14

Nodes of Ranvier: Spaces between myelin on axon with a high concentration of ion channels
Signal jumps from one node to another = Saltatory conduction

Question 15

Structure of Voltage Gated Sodium Channels

Answer 15

Pore & voltage sensor from alpha subunit & auxillary beta-subunit
Alpha subunit: 24 transmembrane regions (4 domains)
Per domain: 6 Membrane spanning segments (S1-S6)
S5-S6: Pore S1-S4: Voltage sensor (S4 positively charged)
Linker between domain 3&4 for fast inactivation

Question 16

Opening & Selectivity of Voltage-Gated-Sodium-Channels

Answer 16

Opening: Membrane potential to more positive → S4 moves to the ec side of the membrane → Pore opens → Na+ inside
Selectivity: Mediated by P-Loops → Neg. Charged AAs attract Na+ → Size limitation (K+ is bigger)

Question 17

Channelopathies of Voltage-Gated-Sodium Channels

Answer 17

Mutations in SCN9A (Coding for NaV1.7)

Primary erythromelalgia: Autosomal dominant, threshold for opening is lower
PEPD: GoF in SCN9A → Almost no channel inactivation
Complete pain insensitivity: Channel does not open (LoF of SCN9A)

Question 18

Voltage-Gated Potassium Channels

Answer 18

Structure: 6 transmembrane regions
Channelopathies: Mutations in KV11.1 → Long QT syndrome type 2 & sudden infant death → Changes not in conductivity but in the amount of expressed channels

Question 19

Voltage-Gated-Calcium-Channels

Answer 19

Structure: Same as NaV, Selectivity filter based on charge
Function: Fusion of the vesicles with the synaptic membrane → NT release