Nerve Conduction Flashcards

1
Q

What is the Nernst Equation?

A

Vm = -(RT/zF)*ln([x]i/[x]o)

or simplified for physiological conditions:

Vm = 61.5*log10([x]i/[x]o) –>for monovalent ion at 37C

Vm = Membrane potential
R = gas constant
T = temperature
z = charge
F = faraday constant
[x]i and [x]o = concentrations in and out of cell
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2
Q

Define the Nernst Equilibrium Potential of an ion

A

The membrane potential at which there is no net transport of that ion across the membrane/there is no diffusion gradient

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3
Q

What is the role of the Na/K pump in generating the Na+ and K+ distribution

A

Na/K pump extrudes 3 Na ions for every 2 K ion it brings into the cell.

The pump serves to maintain high extracellular Na and high intracellular K.

The membrane potential of a cell is much closer to the Nernst equilibrium potential of potassium and chloride compared to that of sodium, so sodium has a tendency to move into the cell, whereas the other two ions have strong opposing forces for their movement across the membrane

In order to prevent too many Na ions invading the cell through leak channels and ruining the electrochemical equilibrium, the Na/K pump extrudes sodium ions (when there is sufficient extracellular potassium)

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4
Q

How is the membrane potential generated? What is the resting membrane potential roughly?

A

The cell has different conductance for different ions. Resting membrane potential roughly -90mV to -65mV.

It has high conductance for potassium ions, which are in higher concentrations inside the cells, and much lower outside the cell (due to the Na/K pump), contributing the most in determining the resting potential. There is a constant leak of potassium ions, which is rectified by inward rectifiers as well as the Na/K pump.

However, there are non selective channels that allow a small conductance of sodium ions, which contribute minorly to the resting potential, more so at low extracellular potassium concentrations. Sodium is in much higher concentrations outside of the cell, so it moves into the cell to partially offset the positive charge leak from the potassium channels, however sodium ions are extruded by the ATP-ase Na/K pump.

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5
Q

Explain the significance of the Double-Donnan effect?

A

Stabilises cell volume by maintaining osmotic equilibrium.

If cell were totally conductive to all ions, then the situation would be as follows:

Inside of cell would be full of anionic proteins and organic phosphates impermeable to membrane, making cell negatively charged

Electroneutrality would be preserved by positively charged ions establishing equilibrium (such as sodium and potassium moving into the cell), and the chloride moving in to account for any charge in-balances caused by concentration gradients. However, this would also increase osmolality intracellularly, as the anions within the cell are stuck there and the ions moving in draw in water. The cell would burst.

If you account for cell’s almost impermeance to sodium and the presence of the Na/K pump, then:

Anions inside cell balanced out by potassium, which move into cell and remain in high concentrations there, but leak out due to conc gradient.

Sodium conductance low, so only small amount of sodium moves into cell down conc and electrical gradient.
Sodium that does leak in is mostly extruded by Na/K pump, which also aids in replenishing potassium concentrations

Double Donnan, as the sodium ion is equivalent to an impermeable cation extracellularly, thus preventing excessive osmolality within cell.

In sum, the anions draw cations into the cell (potassium in) and the sodium draws anions out of cell (chloride out)

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6
Q

What does the constant field equation describe?

A

An aggregate of the Nernst potentials, weighted according to conductance, of the permeable ions in the cell

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7
Q

Which does the Na/K pump contribute most to:
-the Em
-the ion gradients
?

A

Ion gradients, which it establishes in order for the negative Em to be generated

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8
Q

What is an action potential? What elicits one?

A

Rapid (1-2ms) transient in which the membrane of an electrically excitable cell is temporarily depolarised and the Em is displaced by up to 100mV

When a cell is depolarised beyond a threshold potential of around -50mV (due to physical/chemical stimuli), voltage gated sodium ion channels will activate and allow a rapid influx of sodium ions into the cell (as there is a strong electrochemical gradient to do so and conductance is temporarily increased).

The high sodium conductance is temporary - the activation gate/M-gate opens much quicker than the inactivation gate/H-gate closes, so there is only a brief period in between where ions can travel through

However, delayed rectifying potassium channels are also activated, but after the sodium channels, and mass efflux of potassium ions coupled with the spontaneous inactivation of the sodium channels caused a repolarisation. The potassium channels are also delayed in inactivating, so the cell is initially hyperpolarised beyond resting Em.

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9
Q

Which chemicals inhibit voltage gated sodium and potassium channels?

A

TTX (tetrodotoxin) and TEA (tetraethylammonium) respectively

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10
Q

What is the absolute refractory period?

A

The period between inactivation of the sodium channels and the start of the hyperpolarisation, during which there are insufficient channels available to initiate an upstroke

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11
Q

What is the relative refractory period?

A

The period from the start of the hyperpolarisation to the return to resting Em where a larger than normal stimulus is required to elicit a second action potential

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12
Q

Define and describe the process of orthodromic conduction

A

‘One-way’ propagation
At region of excitation, membrane is depolarised
Flanking regions of membrane act as current sinks which draw in the positive charge, leading to electrotonic depolarisation
The region behind the AP will not depolarise at it is still in its refractory period, but the region ahead will if the electrotonic depolarisation brings the Vm above the threshold potential.
Electrotonic spread of depolarisation decays from the site of initiation due to leakage through the membrane

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13
Q

How is excessive electrotonic decay prevented in nerve cells, and hence the speed of signal transmission, increased? (3 points)

A

Concentric wrapping of schwann cell membranes can increase membrane resistance by rendering any leak channels ineffective

Increasing nerve diameter decreases cytoplasmic resistance, as proportionally less cytoplasm is in contact with the membrane, which decreases resistance to flow

Increasing temperature within biological limits will increase diffusion flux (remember that the diffusion coefficient is dependant on temperature and molecular weight) of the ions, speeding up conduction velocity

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14
Q

What is saltatory conduction?

A

The process by which a depolarisation in a node of Ranvier causes a current sink which will elicit electrotonic depolarisation only at the next node of Ranvier (because the intervening membrane is wrapped in myelin and is rendered non-conductive to ions), causing the depolarisation to “jump” between nodes

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15
Q

What are the two passive electrical constants of membranes, and what do they measure? Give their general values.

A

Length constant [lamda] = sqrt(membrane resistance/cytoplasmic resistance)

Time constant [tau] = Rm x Cm, where Rm is membrane resistance and Cm is membrane capacitance

They measure limits of distance or duration that an action potential can travel for before its amplitude is no longer enough to depolarise a segment of membrane to threshold.

Length constant roughly 1-3mm and time constant roughly 1-5ms

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16
Q

Explain the concept of a compound action potential

A

Different types of neurons have different thresholds

Larger diameter, myelinated neurons have lower thresholds, thus the stimulus necessary to induce an action potential in them is smaller.

As the stimulus increases, so to does the type of neuron recruited, with smaller and non-myelinated neurons with higher thresholds generating action potentials.

The compound action potential is the sum of the amplitude of each individual action potential generated by a nerve fibre within a nerve.

17
Q

What differentiates local and general anaesthetics? What gives local this property/

A

Local interferes with specific areas only, numbing that area only and keeping the patient conscious

Local has poor plasma transmission, due to drugs tending to be lipophilic, associating with tissues near to where they are injected

18
Q

How is further localisation achieved when administering local anaesthetics?

A

Use of Bier’s block (exsanguinating site in question and then applying a tourniquet to prevent blood flow into the site)

Use of adrenaline to vasoconstrict arteries at the injection site, delaying the resorption of the anaesthetic by restricting blood flow

19
Q

Compare the local anaesthetics lidocaine and bupivacaine

A

Lidocaine - quick onset of action, shorter lasting

Bupivacaine - slower onset of action, longer lasting

20
Q

What order are nerve fibre types affected by LA?

A

Type C and Ad pain fibres

Then other general sensory fibres (afferents) and then motor fibres (efferents)

21
Q

Give an example and the effect of an anticholinesterase drug. How is it used therapeutically?

A

Neostigmine - drug is a competitive inhibitor of the active site of acetylcholinesterase in the synaptic cleft.
It is used to treat diseases such a myasthenia gravis, an autoimmune disease where antibodies bind to the nAChR, blocking the binding of ACh. By preventing acetylcholinesterase activity, the the concentration of ACh in the synaptic cleft increases, improving chances of it binding to a free nAChR that hasn’t been targeted by antibodies.

22
Q

How are nicotinic and muscarinic cholinergic receptors operated?

A
Nicotinic = ligand-gated ion channel, impermeable to anions and permeable to mono- and divalent cations
Muscarinic = G-protein coupled receptors
23
Q

Where are nicotinic and muscarinic cholinergic receptors distributed ?

A

Nicotinic:

  • NMJ (Nm)
  • autonomic ganglia (Nn)
  • CNS (Nn)

Muscarinic:

  • autonomic ganglia (M1)
  • organs innervated by parasympathetic postganglionic nerve fibres (heart = M2, smooth muscle = M3)
  • CNS (M1)
24
Q

What are the three muscarinic subtypes, and the two nicotinic subtypes? What are their structures, effects and distribution?

A

N are pentameric ligand gated cation channels, with binding sites on the a subunits, mediating excitatory effects on target cells. Each subunit spans the membrane 4 times:

Nm = found in NMJ, 2 a, 1 b, 1 y and 1 d subunits. 
Nn = found in autonomic ganglia, CNS and adrenal medulla, consisting of only a and b subtypes in different ratios

M are single polypeptide chains with 7 transmembrane alpha helical domains. They can be found in the pre- and post-synaptic membrane:

M1 = found in CNS, excitatory [activate inositol phosphate pathway], involved in memory, arousal, attention etc
M2 = found in heart, inhibitory [inhibit adenylyl cyclase pathway, reduce intracellular cAMP], lowers heart rate
M3 = found in smooth muscle and glands, excitatory [activate inositol phosphate pathway] causing contractions and secretions
25
Q

Suggest an antagonist of the mAChR and nAChR

A

Atropine blocks mAChR function

Tubocurarine blocks nAChR function

26
Q

Compare the responses and effects of M and N cholinergic receptors, regarding time and action

A

M is always slow in onset and long in duration - can be either inhibitory or excitatory (~2-20s)

N causes a fast excitatory postsynaptic potential (~30ms)