Far Eastern University – Nicanor Reyes Medical Foundation

PHYSIO – B: SAXITOXIN POISONING – 2020 • Ions Channels

o Sodium has two gates
A 30-year-old woman is brought into the emergency room. The patient had  Activation Gate (M gate) – closed when the cell is
been dining in a local restaurant, and while eating dessert she noted the polarized
following symptoms. Initially there was a tingling sensation that affected the  Inactivation Gate (H gate) – open when the cell is
mouth and lips, but then it spread to the face and neck. Then the tingling polaried
spread down the arms and legs to the fingers and toes. o Potassium only has 1 gate
 Activation Gate (N gate) – closed when the cell is resting
At the hospital the patient reports numbness of the areas that previously o Chloride ions yield to zero net flow = same amount of chloride
tingled and difficulty walking in a coordinated fashion. The patient is asked in, out of the cell
to describe the meal she has just eaten and states that she had shrimp
cocktail as an appetizer, followed by salad, steak with a baked potato and
green beans, and apple pie and coffee for dessert. The patient has no history
of allergic response to shellfish. Her superficial reflexes are almost absent,
and her deep reflexes are markedly hypoactive. An extracellular electrode
is placed on the patient‘s ulnar nerve. Then the palmar surface of the
patient‘s little finger is scraped with the physician‘s fingernail in a way that
should be painful to the patient. The patient cannot feel this stimulus, and
no action potentials are detected in the ulnar nerve. When an intracellular
microelectrode is placed on a sensory nerve fiber in the ulnar nerve, the
resting membrane potential is found to be near -70 mV (normal). When an
action potential is evoked by repeated vigorous scraping of the skin of the
little finger as described earlier, the action potential is slower to rise and of
shorter height than expected from measurements in normal individuals. The
duration of the action potential is normal.

REVIEW
ELECTROPHYSIOLOGY
- Excitable cells – Able to produce electrical activity
- Neurons and skeletal muscles are capable of generating rapidly
changing electrical impulses at their membranes which can be
transmitted as signals along the nerve or muscle membrane ACTION POTENTIAL
- Adequate nerve impulse
MEMBRANE POTENTIAL - Response of excitable cells to threshold intensity
RESTING MEMBRANE POTENTIAL - “All or None” principle: must reach the threshold or the critical firing
- RMP, Steady potential or transmembrane voltage potential) level to have a response, any inadequate stimulus would not result
- Constant electrical activity, nonchanging to any response at all
- Maintained by the Sodium-Potassium Pump - Effective stimulation will result into:
- RMP varies depending on the type of neuron: o Nerves – Conduction of impulses
o Small neurons (nerve fibers) -70Mv o Skeletal Muscles – Contraction
o Bigger neurons (muscles/cardiac) -90Mv
- Greater permeability to potassium and chloride ions STAGES OF THE ACTION POTENTIAL
- Lesser permeability to sodium ions • Resting Membrane Potential – membrane is said to be “polarized”
- Not permeable to intracellular proteins • Local Depolarization or Hypopolarization – Opening of the activation
- “POLARIZED CELL” – more appropriate term to describe the activity gates of Na+ channels causing Sodium influx
of a resting membrane o Until it reaches the equilibrium of Na+ ions
o The closing of the channels is at the level of the peak of action
IONS INTRACELLULAR EXTRACELLULAR potential (AP)
Sodium (+) 10 – 15 135 – 145 • Repolarization – closure of the Na+ inactivation gates and result to
the opening of K+ activation gates resulting to Potassium Efflux.
Potassium (+) 120 – 150 3.5 – 5.0
• Hyperpolarization – There is no immediate closure of K+ channels,
Chloride (-) 20 – 30 95 – 105
this will provide more time for Potassium Efflux and will make the cell
Proteins (-) 100 0.2 more negative until it reaches the equilibrium of K+ ions

TAKE NOTE OF THE FOLLOWING:

• EXTRACELLULAR:
o Major cation: Sodium
o Major anion: Chloride
o Ca2+ are also found outside
• INTRACELLULAR
o Major cation: Potassium
o Major anion: Proteins
• TAKE NOTPOSITIVE OUTSIDE, NEGATIVE INSIDE
• PISO = Potassium located inside, Sodium located outside
• “Tatlo Na PuTo” = 3 Na Po 2
o In Sodium, electrical & concentration gradient tries to push
them IN, but minimally succeed because less conductance
o In Potassium, concentration gradient has a greater effect than
the electric gradient
 Concentration gradient pushes them out
 Electrical gradient let it stay since Potassium is positively
charged & inside cell is negatively charged = attraction

1
 LOCAL POTENTIAL
- Local Response, Local Excitatory State, Graded or Subthreshold
Potential)
- Ineffective stimulation  subthreshold potential
- Only produced localized change
o Can still cause an electrical change but it will not lead to an
action potential but will only change or disturb the RMP
o Different terminologies depending where it is happening:
 End-plate potential (muscles)
 Synaptic Potential (neurons) - EPSP (excitatory) and
IPSP (inhibitory postsynaptic potential
 Receptor potential (sensory receptors)- AKA
“Generator Potential”
 Electronic potential
MANAGEMENT
PATHOPHYSIOLOGY • There is no antidote for Saxitoxin poisoning and the treatment is
SAXITOXIN symptom based.
- It is a potent neurotoxin and the best-known paralytic shellfish toxin • The greatest danger is respiratory paralysis.
(PST). • Close monitoring for at least 24 hours and aggressive airway
- Ingestion of Saxitoxin, usually by consumption of shellfish management at any sign of respiratory compromise should prevent
contaminated by toxic algal blooms, is responsible for the human severe morbidity and mortality.
illness known as paralytic shellfish poisoning (PSP). • Neostigmine and edrophonium have been used to improve muscle
- STX and its analogs are collectively called paralytic shellfish toxins weakness following Saxitoxin intoxication.
(PST) and are considered to cause lethal paralytic shellfish poisoning
• Nonetheless, no clinical trials have evaluated the use of these drugs
(PSP).
for Saxitoxin exposures.
- Saxitoxin are heat stable, acid stable and water soluble; They are
tasteless and odorless and are not destroyed by cooking.
SOURCES:
- This neurotoxin is selective meaning it only blocks the voltage-gated
1. Cell & Electrophysiology Lecture
sodium channels and leaving all other channels functioning normally.
2. Red Tide Poisoning – Related Topic
3. Previous trans & Q&A with friends
MECHANISM OF ACTION
It acts by blocking the voltage-gated sodium channels preventing sodium
influx which relatively prevents depolarization thus there will be no action
potential. The occlusion of the channel’s extracellular pore opening
therefore blocking influx of sodium into the cell which results to the
prevention of impulse transmission. Saxitoxin cross the blood–brain barrier,
and sodium channel blockage in the central nervous system therefore
contributes to its paralytic effects.

RATIONALE OF THE MANIFESTATION

Tingling sensation - Felt from the mouth and lips spreading to the
face and neck and subsequently down to the
arms and legs.
- It is observed that the paralysis is in a
descending pattern.
- Caused by Saxitoxin blocking the voltage
gated sodium channels, there is only a small
amount of Na that enter the cell via the Na
leak channels.
Superficial - End plate potentials are decreased because
reflexes almost the sodium channels are blocked.
absent and Deep - Even though the cell is responsive to Ach,
reflexes markedly sodium still cannot enter which prevents the
hypoactive propagation of action potential thus
Impulse cannot be sent to the muscle and
contraction will not occur.
Normal RMP - Remember that there are other factors that
contribute to the maintenance of RMP. This
includes leak channels, Na-K ATPase pump
and your voltage gated channels.
- Allow us to rule out that K+ channels is not
affected by the poisoning
- K+ ions also a major determinant of the RMP
since it has a greater permeability compared
to sodium
Action potential - The stimulus only generated a subthreshold
slower to rise and potential since the sodium channels are
of shorter height blocked and sodium cannot enter the cell,
the stimulus given is not enough to illicit a
response that will reach the critical firing
level.
- This is why the physician tried to illicit an
action potential by vigorously scraping of the
skin of the little finger.