Chapter 2

Clinical Applications Box: Anesthesia and Neuronal Electrical Signalling (pp. 37 - 39)

○ LOCAL ANESTHESIA: ○ REGIONAL ANESTHESIA: ● GENERAL ANESTHESIA:

■ desensitizes a larger region of
prevents pain sensation in localized parts of the the body causes unconsciousness: absence of sensation
body ■ inject LOCAL ANESTHETICS & muscular relaxation
into the SPINAL CORD to
prevent pain sensation where
still conscious procedure will be performed used for major surgical procedures (long duration
■ think the 50% of mother’s &/or substantial loss of blood)
apply or inject LOCAL ANESTHETIC onto/into the epidural space of spinal
target tissue canal during childbirth in think a really big surgery you don’t want to be
the US to prevent pelvic awake for
The topical application makes local anesthesia pain
highly restricted in its range of action ■ Usually conscious but Can be
sometimes receive SEDATIVE
agent (tranquilizer)
■ think your mouth during a INTRAVENOUS ANESTHETICS → inject into
dental procedure (injection of circulatory system
procaine into mandible to to ↓ anxiety or induce sleep
block AP conduction in the Can be induced by injection of higher doses of
inferior alveolar nerve) SEDATIVES enhance the activity of postsynaptic SEDATIVE agents
GABA receptors found at most inhibitory synapses
What do LOCAL ANESTHETICS do? → stronger synaptic inhibition → ↓ neuronal
don’t prevent pain sensation so often administered
activity → sedation
with ANALGESIC AGENTS
Block Na+ channels → blocks AP propagation
along PERIPHERAL NERVES = loss of sensory Types of SEDATIVES:
ex fentanyl
perception:NUMBING
1)Benzodiazepine
Acts on receptors for OPIATE PEPTIDES to
alleviate pain
Replaced barbiturates as they are lethal at high
Ex: Procaine and lidocaine doses
Longer acting OPIATE RECEPTOR DRUGS are
used for postoperative analgesia
ex. Valium (diazepam): for anxiety, alcohol
withdrawl and seizures
ex. morphine

2)Imidazopyridine
Ketamine is a drug that blocks the
NMDA-typeGLUTAMATE RECEPTORS at
Type of hypnotic agent to induce sleep excitatory synapses

ex. Ambien (zolpidem) But also works on GABA & OPIATE RECEPTORS

3)Propofol ↓ excitatory synaptic transmission

Also blocks Na+ channels in a similar way to Use is limited b/c of side effects like production
LOCAL ANESTHETICS of hallucinations

INHALATION ANESTHETICS→ inhale through

respiratory system

Are volatile liq that vaporize at room temp to then

be inhaled

Diethyl ether - not used anymore b/c highly

flammable

Halothane & isoflurane - more widely used

open the 2 pore K+ channels that create the

resting potentials → hyperpolarize resting
membrane potential of neurons → more difficult to
fire an AP

Showed how valuable these clinical agents are and emphasizes the importance of neuronal electrical signaling for the function of the nervous system

Electrochemical Equilibrium in an Environment with More Than One Permeant Ion (pp. 42-43)

Context
Consider a situation where there was 10 mM K+ and 1 mM Na+ inside the cell and 1 mM K+ and 10 mM Na+ outside
the cell:

- With the Nernst Equation we can see that

- If the membrane only permeable to Na+ the potential is +58mV.
- If the membrane is only permeable to K+ the potential is -58mV.…but…

What if the cell is permeable to both K+ and Na+? → that’s where the Goldman Equation becomes useful.

- b/c potential also depends on the relative permeabilities of the membrane to the ion.
- the Nernst Equation depends only on the concentration gradients of the permeant ions
- so to describe the membrane voltage across the membrane taking into account both the concentration
gradient of ions and the relative permeabilities of the membrane to those permeant ions
- David Goldman developed the Goldman Equation
- where
- V is the voltage across the
membrane in reference to the extracellular region
- Px indicates the permeability of the membrane to each ion.

- Essentially the Goldman Equation is an extension of the Nernst equation

- this is evident if we take the situation where the membrane is permeable only to one ion → we end up
with the Nernst Equation
- the difference is that there is not valence factor (z) in the Goldman Equation
- this has been taken into account by inverting the concentrations of negatively changed Cl-
relative to the concentration of the +’vely charges ions. (-log(A/B) = log(B/A)

What does this show us?

- Considering the same concentrations as above:

- if the membrane only permeable to Na+ the potential is +58mV.
- if the membrane is only permeable to K+ the potential is -58mV.
- if the membrane is not permeable to Cl- but is permeable to both Na+ and K+ then the potential is
some intermediate of the potentials of situations where the membrane is only permeable to Na+ or K+.
- if the membrane is not permeable to Cl- but is equally permeant to K+ and Na+ the potential would be
0mV.
- What if permeability of an ion fluctuates?
- describes an AP
- in the RESTING state the PK is much larger than the PNa and as such the RESTING POTENTIAL
is negative (closer to the potential of if the membrane was only permeable to K+)
- as membrane potential depolarizes in the RISING PHASE the PNa increases causing the
membrane potential to become more and more positive.
- at THRESHOLD the AP is triggered
- then as membrane permeability to K+ is restored the membrane
potential quickly returns to its negative RESTING level.

Box 2A: The Remarkable Giant Nerve Cells of Squid (p. 45)

Why squid axons?

- they can be up to 1mm in diameter

- which is about 100 to 1000 times larger than the diameter of mammalian axons
- the larger size allows for experiments to be done & better observation of the mechanisms of synaptic
transmission. They also take out the cytoplasm and measure its ionic composition.> decrease rA or
axonal resistance
Who discovered this?

- John Z Young at University College London discovered the giant nerve cells of squid and the corresponding
giant synapse

Why did squid neurons evolve to be giant?

- giant neurons evolved in squid (& as we learned many other invertebrates too) to enhance their survival
- → larger axonal diameter allowed faster AP conduction
- specifically, these neurons are part of a neural circuit that activates the contraction of the mantle
muscle that produces a jet propulsion effect allowing squid to move away from predators very
quickly.

Why does it matter?

- these experiments on the extraordinarily large neurons of squids provided the initial insights into how ion
concentration gradients & changes in membrane permeability provide electrical signals

Chapter 4
Box 4B: Toxins That Poison Ion Channels (p. 71)
Clinical Applications Box: Neurological Diseases Caused by Altered Ion Channels (pp. 75 - 77)

tetrodotoxin: puffer fish toxin

blocks Na+ channels so no APs fire
saxitoxin: dinoflagellates - shell fish, blocks Na+ channels
alpha toxins: slow inactivation of Na+ channels, prolongs AP
Beta toxins: causes na+ channels to open at potentials much negative than normal and causes uncontrolled AP firing

epilepsy ataxia migraines pain deafness

recurrent seizures;
rhythmic firing of large
groups of neurons
mutations: 5 Na+
channels, 7 K+
channels, 2 Ca++
channels
slowing of Na+ channel
activation
voluntary movement loss; mutations in VG Ca++ increased pain Ca++ channel is
cerebellar function channels, increase perception: unique Na+ disrupted and no influx
impairment amount of current channel on dorsal root results
defects in VG K+ flowing through ganglia progressive hearing loss:
channel, impairing increases amount of blindness
repolarization Na+ coming through mutations in K+ channel
blindness
reduction in Ca++ decreased Ca++
channel current flow channels as they are
truncated

S cones make up only about 5% - 10% of the cones in the retina, and they are virtually absent from the center of the fovea. (S, M, L-
Blue,green, red)

M and L types are the predominant retinal cones, the ratio of M to L varies considerably from individual to individual, but the difference doesn't
impact colour Perception

normal people see trichromatically

colour blindness: dichromatic

protanopia: red perception impairment (L)
deuteranopia: green perception impairment (M)
tritanopia: rare, yellow-blue colour blindness
anomalous trichomats: three light sources are needed to make all possible color matches