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36 Cards in this Set

  • Front
  • Back

Signalling in nervous system

Binary code, either on or off

Neuron signalling

May have to travel long distance, along nerve axons from 1 place to another


Involves rapid changes in the membrane potential

The firing of a neurons refers to?

rapid depolarization by opening of voltage-activated (cations/opearated) channel

Voltage activated (cation/operated) channels

cation-selective pore opens when Vm changes

Types of channels

Voltage gated


Intracellular ligand gated


Extracellular ligand gated


Stress activated


Initial depolarisation

Initial change in membrane potential (depolarisation) -> reaches the threshold -> large voltage channels open -> AP generated

Graded response

Opening of small capacitance cation receptor channel (NAchr at neuromuscular junction)



Graded response can summate



Different amplitude



If the sum up of the graded potential reaches a threshold lv of depolarisation, the voltage activated Na channel opens -> AP generate



The stimulus is proportional to the AP

Why is AP generation short-lived?

Because K channel soon opens -> reverse the change in Vm

Depolarisation

Opening of voltage gated Na channel after the graded potential reached the threshold

Repolarisation

closure of voltage gated Na channel


Opening of voltage gated K channel

Hyperpolarisation

Voltage gated channel remain open after the potential reaches resting level => refractory period

Refractory period

After the potential reached the resting level, the voltage gated channel remains open so another AP cannot be generated

Permeability of Na and K during depolarisation

Na permeability rapidly increases


K permeability gradually increases

Permeability of Na, K during repolarisation

K permeability rapidly increases, and once opened, remained for a long time (refractory period)


Na permeability rapidly decreases.

If the Na pump is blocked by ouabain, what happened?

The magnitude of AP will decrease progressively until the membrane Na gradient decreases to the point where AP fail



Many still be able to be generated

Blocking voltage activated Na channel by tetrodotoxin (TTX)

Abolished AP -> no graded post synaptic potential

Why does AP not summate?


Because they demonstrate refractoriness


AP code info.by frequency, not amplitude



The frequency limit imposed by the refractory period due to the inactivation of voltage activated Na channel


Propagation of AP along axon

At rest: the membrane is polarised


Depolarisation due to AP sets up local circuit currents in both direction


In backward direction, the Na channel are in refractory phase -> another AP can't be generated -> AP moves forward

Factors affecting the speed of AP conductance

Myelination, Temperature, axon diameter

What is it about axon diameter that could affect the speed of AP conductance?

membrane has high capacitance compared with cytosol


The fatter the axon, the lower the resistance length ways, the faster the conductance

What is it about myelination that could affect the speed of AP conductance?

insulating the axon membrane with myelin is more efficient to increase AP conductance velocity than increasing the diameter

Oligodendocytes

Wrap multiple CNS axons with myelin and Schwan cells

Where are the ion channels on the axon?

Nodes of Ranvier


Saltatory conductance

As ions channels are located on the node of Ranvier therefore the AP jumps from node to node

Mammalian conduction velocity

Require the lowest threshold: A alpha, largest threshold: C fibre


Largest diameter: A alpha, smallest diameter: C


Fastest conduction velocity: A alpha, slowest conduction velocity: C fibre

Mechanism of action of Local Anaesthetics

Block the conductance of APs in sensory nerves by blocking the voltage activated Na channel from the inside

Properties of Local anaesthetic

It needs to diffuse through axon membrane so it must be uncharged at plasma pH



Charged molecules block the channel

Unionised and ionised drugs and their effects

Unionised drugs are more readily to pass through the lipid cell membrane => reach the target more quickly



Ionised drugs are not readily passed back through the membrane => trapped => exerts the effect (binds to voltage gated Na channel

Differential sensitivity to Local anaesthetics

myelinated and thicker axons are more difficult for LAs to penetrate


C fibre carries pain signal -> easier to block than motor nerve A fibre because it is unmyelinated and thin


LAs reduce pain at lower dose, but if overdose, they affect other sensation and motor function because they affect other nerve

Application of LAs: surface anaesthesia

sprays on mucus membrane, cornea drops


Lidocaine, tetracaine


Not generally effective for skin but EMLA produce LA in abt 1 hr

EMLA

eutectic mixture of lidocaine and prilocaine

LAs application: Infiltration

injection to the tissues -> reaches nerve


Most LAs


Minor surgery


Adrenaline might be added, vasoconstrictor -> prevent diffusion away from site)


Not for finger and toes -> risk of ischaemia


LAs application: I.V regional

Injected distal -> pressure cuff (stop blood flow)


Limb surgery


Prilocaine, lidocaine


Danger of systemic toxicity if release the cuff prematurely

LAs application: nerves block

injection closes to nerve trunks -> reduces sensation peripherally


Surgery, dentistry

LAs application: spinal

Injection to subarachnoid space (containing CSF)


Depress spinal roots and cord


Surgery: abdomen, pelvis, legs


Glucose is added to increase the density -> limit spread due to tilting patient during the operation


Risk of CVS effect, repiratory depression -> spread to brain -> avoid tilting


Post-op urinary retention due to block of pelvic autonomic outflow


LAs application: epidural

injection to epidural space blocking spiral roots


Lidocaine, bupivacaine


Spinal applications, painless childbirth