Outline

Resting membrane potentials

Action potential
RMP
Definition
It is a steady state potential which exists across
the cell membrane
It is always hyperpolarized
RMP
SA node -60 mv
Atrium -90mv
Ventricles -90 mv
Skeletal muscles -70mv
Smooth muscle -60mv
Peripheral nerves -70 mv
RMP
Determinants of RMP?
Electrolyte
Na/K ATPase pump
Intracellular protein
Gibbs Domann
Concentration gradient
RMP
Electrolytes / concentration gradients

ICF ECF
Na 10-20 135-145
K 150 3-5
Cl 10-20 110
100x
RMP
The membrane is more permeable to Na and K ,
so these ions tend to leak across the membrane
down according the concentration gradient
The membrane is 100 times more permeable to K
So, there is more K is lost from the cell than Na
enters to the cells
Therefore, net result- larger amount of positive
charges has left the cell than entering it.
Thus, that is why cell are semipermeable
Na/K ATPase pump
It pumps more Na out from the cell than K is
pumped in
( 3Na out: 2K in)
It maintains the RMP
Intracellular protein
There are negatively charged intracellularly
So RMP is negative
Gibbs- Donnan effect
The Donnan Effect
Which fluid compartments are high in protein?
intracellular fluid
plasma
Which fluid compartment is low in protein?
interstitial fluid
Fig. 1-27 Ganong
The Donnan Effect
Proteins are impermeant polyanions.
Proteins are impermeant to the membrane.
due both to size and charge
Most proteins have a net negative charge.
This negative charge is balanced by cations, typically
monovalent cations.
K
+
for intracellular fluid
Na
+
for plasma
Fig. 12.11
The Donnan Effect
When Donnan and Gibbs analyzed the situation
mathematically, they showed that in and out
could not be in electrochemical and osmotic
equilibrium at the same time.
(see Ganong)

As a result of the osmotic imbalance, water will
flow into a compartment (cytosol, blood plasma)
that contains more protein.
The portion of the osmotic pressure that is due to the
effects of protein is called colloidal osmotic pressure.
The problem:
Because of the
Donnan effect, cells
will swell and burst.

The solution:
For animal cells, the
sodium pump solves
the problem.
Na
+
pumped out
Cl
-
follows Na
+
H
2
O follows NaCl

Alberts et al.,
Molecular Biology of the Cell
Animal cells must
have sodium pumps.
Nernst Equation
at equilibrium these opposing energies
must be equal
therefore by rearrangement, viz.
Calculate one ion

o
i
m
K
K
zF
RT
E
(

+
(

+
= ln
E
K
K
K
i
o
=
+

(
+

(
615 . log
GOLDMAN CONSTANT-FIELD EQUATION
V = RT In P
K+
[K
+
]
o
+ P
Na+
[Na
+
]
o
+ P
Cl
- [Cl
-
]
i

F P
K+
[K
+
]
i
+ P
Na+
[Na
+
]
i
+ P
Cl
- [Cl
-
]
o

The magnitude of the membrane potential at any given time
depends, of course, upon the distribution of Na+, K+ and Cl-
and the permeability of the membrane to each of these ions.
It calculate 3 ions
THE ACTION POTENTIAL
An action potential is the sequence of
changes in the membrane potential that
occurs during the transmission of an
electrical signal along the cell membrane,
as measured at a specific point on a nerve
or muscle cell membrane.
d
e
p
o
l
a
r
i
z
a
t
i
o
n

r
e
p
o
l
a
r
i
z
a
t
i
o
n

~ 1 ms
Fig. 12-13
Fig. 2-6
Ganong
The Action Potential
skeletal muscle fibers
axons of neurons
Fig. 12.13
Fig. 12.12
Fig. 11.1
Phase 1 whn a nerve is stimulated, it initiates
the ligand-gated Na channels, n there will be
influx of Na ions initiating depolarization
Phase 2 whn the depolarization reaches the
threshold potential ard -55mV, it opens up the
voltage gated fast Na channels
Phase 3- massive influx of Na ions
Phase 4 the potential overshoots the
isopotential line to ard + 30mV ( positive spike
AP)
Phase 5 Na channels closed, K channels
open , and there will be K efflux
Repolarization
Phase 6 due to continuation of K efflux ,
there will be hyperpolarization

Action Potentials
Characteristics:

1. Stereotypical size and shape
2. Propagation to adjacent sites
3. All-or-none response
Action Potentials:
Characteristics
1. Stereotypical size and shape

Each action potential for any cell type looks identical.
It depolarizes to the same potential.
It repolarizes back to the same resting potential.
-70 mV
0 mV
1.0 2.0
Action Potential
Resting membrane potential
Time (milliseconds)
V
o
l
t
a
g
e

Action Potentials :
Characteristics
2. Propagation to adjacent sites

The action potential moves along the axon in a wave of
changing membrane potential.
After an action potential, the membrane is in a
refractory state so the propagation is in one direction
only.
This action potential propagates from one end of the
nerve to the other.

A
B
C
-
+
-
+
-
+
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
Active
region
Propagation of action potentials
(in unmyelinated fibres)
Myelin sheath
Action potential
Node of Ranvier
-
+
-
+ +
-
+
-
+
- -
+
Saltatory conduction in myelinated fibres
2
4
6
8
myelinated
unmyelinated
Effect of myelination on speed of propagation
Fibre diameter (m)
C
o
n
d
u
c
t
i
o
n

v
e
l
o
c
i
t
y

(
m
/
s
)

1 2 3 4
Action Potentials :
Characteristics
3. All-or-none response

If an excitable cell is depolarized to threshold in a
normal manner, then the occurrence of an action
potential is inevitable.
On the other hand, if the membrane is not depolarized
to threshold, no action potential can occur.

-100
-50
0
+50
Threshold potential
Resting membrane potential
Increasing subthreshlod stimuli
M
e
m
b
r
a
n
e

p
o
t
e
n
t
i
a
l

(
m
V
)

Time |----------------|
1 ms
All-or-none action potential
Compound action potentials

Peripheral nerves contain a mixture of fibres

Classified according to
Function
Diameter
Conduction velocity
Table of compound action potential
Fibre Function Diameter
(m)
Conduction
velocity
(m/s)
A



Skeletal motor, joint position
Touch, pressure
Muscle spindle motor
Pain, temperature touch

10-20
5-10
3-6
2-5
60-120
40-7-
15-30
10-30
B Preganglionic autonomic 1-3

3-15
C Pain 0.5-1

0.5-2
V
o
l
t
a
g
e


(

V
)

Time (ms)
Compound action potential
A



B
C

The electrical signals generated by the action
potentials can be sensed using skin or needle
electrodes placed near the muscle. This is the
basis of electromyography.


Electroencephalography
Is recording of spontaneous activity of the
brain
Generated by pyramidal cells in cortical layers
1, 2 and 5
Its a summation of excitatory and inhibitory
postsynapticpotentials in pathways running
from thalamic nuclei to cortex.
Eeg
4 types of waveform :

Occurs Hz Voltage
(microv)
beta Fully awake
Maybe also produced by volatile
and IV anaes
Precentral cortex
15-25 20
alpha Transitional
Awake,relaxed with eyes closed
Occipital cortex
10-15 20-50
theta Sleep
Occurs in children, elderly
May indicates dysfx of drugs
1-5 20-50
delta Occurs during sleep during stage
3 and 4 of NREM
0.5 1 >50
Application of EEG
In tumor and epilepsy shows high voltage
spike waves
Cerebral infarcation low volatge and low
frequency
Thiopentone, propofol, etomidate, and
volatile agents produce initial fast frontal
beta, then frontal alpha spikes with high
ampitude , then 1-3 HZ delta burst
suppression with high amplitude , then no
isoelectric EEG
Application of EEG
Ketamine frontal rhythmic delta with high
amplitude, then intermittent, polymorphic
delta with large amplitude interspersed with
low amplitude beta. NO EEG silence
BZD- no burst suppression and no isoelectric
EEG
Opiods dose related low frequency and
high amplitude, no isoelectric EEG
Sleep
Is a state of unconsiousness from which a
person can be aroused by a sensory
stimulation
Involves decrease activity of RAS(reticular
activation system)
2 stages :
NREM or slow-wave sleep(4 stages)
REM( tonic and phasic)
Stages of sleep
Influence of anaesthesia and
surgery during sleep
NREM anaesthetic stages
REM- post op complication
Why????
In NREM, mainly is by parasympathetic
In REM, esp during the phasic phase is mainly by
sympathetic and is predominant during post op Day1
In REM, thr wil be impaired resp fx
Maldistribution of ventilation , impaired V/Q matching
which lead to arterial hypoxemia
Thus, MI, cerebral impairment and hypoxemia is
common post op Day 1

Depth of anaesthesia for
awareness
Awareness
Inadvertent return to conciousness during a supposed
GA with or without recall
Techniques that monitored depth of
anaesthesia:
MAC
BIS(bispectral index)
Vital sign
Entropy
TCI/TIVA ( plasma concentration drug)
IFT(isolated forearm tech)
BIS
It monitors record raw EEG which alters
anaesthesia and after processing produces a
dimensionless number from 0 -100 which is
an index of probability that the pt is aware
Put at the frontal lobe
Limitation of BIS
Site of operation
Cant do in children
Organic brain lesion
Psy problem
Drugs like etomidate and ketamine
Costly
Artifacts by surgery
diathermy/cauterization/vibration