lecture 8: disorders of excitability Flashcards
the extracellular fluid
- the properties of ECF are tightly regulated and essential to life
- in extreme environments, abnormal dietary conditions, high work rates, some medications and many health problems the ECF composition may deviate from normal values
potassium ECF abnormalities
- hypokalemia
- hyperkalemia
hypokalemia
- low ECF potassium
- loss from digestive tract (vomiting, diarrhea)
- loss from body fluid (excessive sweating, diuretics)
- reduced nerve cardiac excitability due to MP being more negative
- weakness and hypoventilation, fatigue, cramps, arrhythmia
hyperkalemia
- high ECF potassium
- inability to clear K (kidney disease), addisons disease (low aldosterone), K-rich diet, tissue trauma, many medications (eg: ACE inhibitors, NSAIDs)
- MP more positive, prolonged depolarization (depolarization block)
- weakness, fatigue, life threatening cardiac arrhythmia (VF, asystole)
what does the cell membrane potential depend on
- conc gradients of ions
- relative permeability of membrane for ions
resting membrane potential in terms of ions
its largely a K+ diffusion potential, because of higher resting permeability of membrane to K+ than Na+
neurological diseases as a result of a loss of myelin
- multipel sclerosis (CNS)
- guillain Barre syndrome (PNS)
symptomatic consequences of loss of myelin
- vision
- movement and muscle control
- sensation
- speech
- fatigue
- incontinence
what happens in unmyelinated axons
- the major ion channels that facilitate depolarization and repolarization (Na and K channels respectively) are present on the entire membrane surface, so the wave of depolarization can propagate along the membrane
what happens in myelinated axons
- have high density VG Na and K channels at and near the nodes of ranvier, but few Na channels under myelin
- there are K channels under myelin, but myelin normally “insulates” the axon by preventing current leakage through them
- this ensures passive spread of depolarization is still strong enough to bring the membrane to threshold at an adjacent node
- normally have “leak” channels under myelin
what is the effect of a loss of myelin
- permits current “leakage” at internodes, reducing effective distance of spread of the wave of depolarization
- AP conduction is slowed and transmission may fail
local anaesthetics
- typically applied to peripheral nerves to inhibit transmission of noxious stimuli to CNS
noxious stimuli
typically arise as a result of tissue damage and are transmitted along “pain fibres” in peripheral nerves
what happens if APs encoding painful sensations cant reach the CNS
pain is not percieved
what is the basic target of local anaesthetics and toxins
- AP conduction is critically reliant on opening of VG Na channels to generate the depolarization phase of the AP
- if VG Na channel opening could be inhibited, AP generation would be inhibited
how do local anaesthetics work
- LAs are lipophilic so can diffuse into cell
- in cell, they bind open VG Na channels and stabilize the inactivated state
- further Na entry is inhibited
- axon cannot become depolarized
toxins
= naturally occurring nerve blockers
- can typically bind ion channels and hold them in the open or closed state
- either way, AP conduction is inhibited, so the symptoms of intoxication include paralysis, loss of sensation, autonomic effects (eg: loss of normal homeostasis)
- given the importance of AP generation and conduction, it is not suprising that many toxins are extremely poisonous and can be fatal at low doses
examples of well known toxins that interact with nerve membrane ion channels
- tetrodotoxin = Na channel blocker
- saxitoxin = Na channel blocker
- batrachotoxin = Na channel opener
- charybdotoxin = blocks some types of K channel
- dendrotoxins = block VG K channels
- Apamin = blocks some types of K channel
