Neurophysiology - RMP and Action Potentials Flashcards
What is membrane potential of a cell
The electrical voltage of its interior relative to its exterior
What is resting membrane potential, normal RMP in excitable and non-excitable tissue and what is an action potential
Resting Membrane Potential (RMP) is the electrical voltage difference of a cell membrane of its interior relative to its exterior at rest.
Normally
- Nerve : -70mV
- Cardiac and Skeletal muscle: - 90mV
- Non-excitable cells: -30 mV
- Small intestine: -40 –> -70 mV
An action potential is a transient change in membrane potential from RMP to a positive value. The cell membrane is then describe as being depolarized.
Under what circumstances will there be a negative membrane potential
Under what circumstances will there be a positive membrane potential
Negative: When there are more positively charged ions outside the cell versus inside the cell
Positive: When there are more positively charged ions inside the cell versus outside the cell.
Why is there a charge difference between the inside and the outside of the cell creating a membrane potential?
Variation in the distributions of ions across the cell membrane affected by:
- Selective permeability of cell membrane
- Negatively charged intracellular proteins
- bind cations and repel anions
Which three major ions influence the resting membrane potential
- K+
- Na+
- Cl-
Compare the intracellular and extracellular concentrations of Na and K and indicate why these different concentrations exist
The different concentrations are established by the Na/K ATPase pump.
K+
Inside 150 mmol/L
Outside 5 mmol/L
1. Phospholipid bilayer is impermeable to charged K+
2. K+ leak channels exist that permit K+ to pass down conc. gradient: from ICF to ECF
Na+
Inside 20mmol/L
Outside 140 mmol/L
1. Phospholipid bilayer is impermeable to Na+
2. At RMP Na channels are closed leaving the resting cell membrane impermeable to Na
How do intracellular Cl- concentrations affect membrane potential
They don’t. Membrane potential passively influences Cl- movement.
What does the Nernst equation calculate?
For a particular membrane-permeant ion X (e.g. K+), the Nernst equation calculates the contribution that that ion makes to the overall resting membrane potential at X’s electrochemical equilibrium
Write the Nernst Equation and state what each variable and symbol stand for
Ex = RT ln [X]o
__ ___
zF [X]i
Ex: Nernst potential for a particular ion (mV)
R: Universal gas constant (8.314 J/(K mol)
T: Absolute temperature (K)
F: Faraday constant (the electrical charge per mol of electrons 96500C/mol)
[X]o: Ion concentration outside
[X]i: ion concentration inside
ln = log e (natural logarithm)
What is the Goldman-Hodgkin-Katz equation?
The equation used to calculate the membrane resting potential taking into consideration the intracellular and extracellular concentrations of Na, K and Cl- as well as the membrane permeability to these contributing ions.
How does hyperkalaemia affect nerve conduction
PRINCIPLE: THE MORE POTASSIUM THAT LEAKS FROM ICF TO ECF THE MORE DEPOLARIZED THE RMP.
Hyperkalaemia –> reduced K+ leakage into ECF (reduced gradient) i.e. Nernst potential for K+ (the determinant of RMP) goes from -90 mV to -80 mV (depolarised). –> closer to threshold potential –> spontaneous generation of action potentials more likely –> VF etc.
How does hypokalaemia affect nerve conduction
PRINCIPLE: THE MORE POTASSIUM THAT LEAKS FROM ICF TO ECF THE MORE DEPOLARIZED THE RMP.
Hypokalaemia –> Increased K+ leakage into ECF (increased gradient) i.e. Nernst potential for K+ -90 –> -100 mV which is hyperpolarized –> further from threshold potential –> more difficult to generate and propagate action potentials –> Muscular weakness and ECG changes.
How do hyper and hypoNa+ affect nerve conduction. Explain seizures in severe hyponatraemia
As the cell membrane is relatively impermeable to Na –> changes to [Na] have minimal effect on RMP.
In severe hyponatraemia reduced ECF osmolarity causes cells to swell –> dilution of IC K+ –> reduced outward movement of K into ECF and depolarization of RMP –> closure to threshold –> increased spontaneous initiation and propagation of action potentials –> seizures.
Explain the mechanism of tetany and paraesthesias in hypocalcaemia
Ca++ maintains normal function of Na+ channels.
HypoCa+ –> activation Na channels –> more negative threshold potential (closer to RMP) –> spontaneous depolarization of neurons –> tetany and paraethesias
Explain why Ca++ is given for cardioprotection in hyperkalaemia?
Calcium has a membrane stabilizing effect due to the ‘surface charge hypothesis’.
Ca+ binds to the outside of the cell attached to glycoproteins –> increasing positive charge on the extracellular side of the membrane (impermeable to Ca+) –> hyperpolarization of RMP.
Define an action potential
TRANSIENT REVERSAL of membrane potential that occurs in EXCITABLE CELLS (neurons, muscle cells, endocrine cells).
‘ALL OR NOTHING EVENT’ i.e. only if the stimulus cause membrane depolarisation that breaches the AP threshold potential.
AP’s allow RAPID SIGNALLING within excitable cells over relatively LONG DISTANCE.
Which part of the neuron does the action potential start and why
At the axon hilock as it has the lowest threshold owing to its high density of voltage-gated Na channels
What is the Nernst equilibrium potential for Na and K. Contrast these values with the voltage of the RMP and the threshold potential
Na is + 55mV
K is - 90 mV
RMP is -70 mV (close to K due to K leak channels)
Threshold is -55 mV
Why is there no action potential if the threshold potential is not reached
Stimulus too small so Na influx is exceeded by K + efflux through K+ leak channels
What causes the initial upstroke of the action potential in nerve cells and what terminates this upstroke
Large stimulus –> breach threshold potential –> opening Na channels –> depolarization –> further opening of Na channels –> depolarization –>
However, when the AP reaches its theoretical maximum
- Inactivation of Na channels occurs
- Delayed opening of Voltage gated K channels –> K + efflux –> repolarization
What causes after-hyperpolarization
Gradual closure of Voltage gated potassium channels
Draw the action potential
Page 222 chambers
How is the AP propagated
- IC surface of membrane normally negatively charged
- Following AP a portion of the cell membrane depolarizes
- IC surface becomes positivel charged
- ion movement at verge of positively charge IC membrane surface results in depolarization of neighbouring portions of the membrane and propagation
What factors affect the velocity of the action potential conduction
- AXON DIAMETER: wider –> lower resistance
- MYELIN
- –> Transmembrane resistance increased –> faster conduction
- –> Transmembrane capacitance –> decreased –> faster conduction
- –> Nodes of Ranvier and saltatory conduction –> faster conduction - TEMPERATURE: Increase temperature –> more rapid opening of Na channels –> faster velocity
What cells produce myelin in the CNS vs PNS
CNS –> oligodendrocytes
PNS –> Schwann cells
Summarise the effects of myelin on action potential propagation
- Increased transmembrane resistance (harder for current to escape nerve into ECF)
- Reduced membrane capacitance (easier to alter polarity)
- Saltatory conduction: nodes of Ranvier (densely packed with Na channels): AP ‘jumps’ node to node
What is the conduction velocity of an AP in a myelinated vs an unmyelinated neuron
Unmyelinated: 2 m/s
Myelinated: 120 m/s
What are two important autoimmune disease that lead to destruction of the myelin sheath in the CNS and the PNS
CNS - Multiple Sclerosis
PNS - Guillain-Barre Syndrome
What is the difference in AP conduction in an unmyelinated versus a demyelinated (MS and GBS) neuron
Demyelinated –> demyelinated neurons have densly packed Na channels at the nodes of Ranvier but the demyelinated portion have inadequate sodium channels to reliably conduct AP –> failure of conduction
Unmyelinated: AP conducted slower but reliably as there are adequate Na channels along the length
Describe the functional classification of nerve fibres
Include diameter/speed/myelination/ sub classification and anatomical location
A alpha - EXTRAFUSAL MOTOR - 20um - 120m/s - myelinated - Least affected by local anaesthetic (LA)
A alpha - Sensory 1a PROPRIO. - 20um - 120m/s - myelinated - Mild affect LA
A alpha - Sensory 1b PROPRIO. - 20um - 120m/s - myelinated - Mild affect LA
A beta: Sensory II - touch/pressure -10um - 60m/s - myelinated - Mild affect LA
A gamma: INTRAFUSAL MOTOR - 5 um - 30 m/s - myelinated - Mild LA affect
A delta: Sensory III - pain/temp - 5 um - 30 m/s - myelinated - Moderate LA effect
B - Preganglionic ANS fibres - <3 um - 10 m/s - myelinated - Severe affect LA
C - Dorsal root) - Sensory IV - Pain/temp/touch - 1 um - 2 m/s - unmyelinated - Severe affect LA
C - Postganglionic SNS - 1 um - 2 m/s - unmyelinated - Severe affect LA
Explain the mechanism of action of local anaesthetics
- Unionized (bases ionize at pH below pKa) portion move into neuron
- Ionized within neuron (lower IC pH) –> cannot diffuse out into ECF
- Block inner surface V gated Na channels in their refractory state
- Prolongation of absolute refractory period
Which nerve types are most to least sensitive to local anaesthetics and what are the clinical effects of this
Small diameter and myelinated fibres
Overall clinical effects: most sensitive to least:
- A delta (fast pain and thermo) (Intermediate thickness + myelinated)
- B fibres (Preganglionic ANS)
- A alpha (extrafusal motor), A beta (touch/pressure/proprio), A gamma (intrafusal motor)
- C fibres (slow pain) (most resistant)
What is the absolute and relative refractory period
Absolute refractory period is the period immediately after and action potential where a further action potential cannot be triggered regardless of the size of the stimulus.
- inactivated v gated sodium channels
Relative refractory period is the period after the absolute refractory period where only a stimulus of increased size can trigger a further action potential.
- Both leak K channels and V gated K channels are open –> therefore a greater stimulus is required to counteract the increased K+ efflux.
Why is the refractory period important?
- Ensure unidirectional propagation of action potentials
2. Limits frequency of APs generated in a given time period
