Lecture 2
- Membrane potential (Vm)
Voltage across membrane at any moment
When cell is at rest, it is called resting membrane potential
RMP is about -70 mV which means it isn’t fully at rest even when
asleep
- ICF vs ECF
ICF refers to intracellular fluid
ECF refers to extracellular fluid
The cell membrane is impermeable to any particles which are
hydrophilic
The typical nerve cell is more negatively charged relative to ECF
area.
The -70 RMP is crucial for the cells’ ability to generate and
transmit signals
High concentration of K+ inside the cell and Na+ outside the cell,
creating a gradient
Gradient maintained by ion pumps
- Movement of Ions
The membrane is selectively and freely permeable to K+
Movement of K+ from ICF to ECF creates negativity in the ICF
Ion pump uses ATP to pump AGAINST concentration gradient to
maintain gradient. This part is important for excitability of
neurons and transmission of signals.
With ICF being negative, it starts to attract K+ back into the cell
and reach equilibrium
IN THE NERVE CELL, EQUILIBRIUM IS ACHIEVED WHEN THERE IS 0
NET MOVEMENT OF K+ IONS, CALLED EQUILIBRIUM POTENTIAL
(Eion) (at -80 for K+)
,- Movement of ions drive
Driven by electrical potential difference and concentration
gradient
- Generating electrical potential difference
Requires
1. Membrane permeability
2. Selectivity of membrane
3. Concentration gradient
- How ions move
Altering charge distribution around membrane results in
movement across membrane, affecting bulk concentration
Difference between Vm and equilibrium of ion (Eion) drives ion
across membrane
K+ movement is affected by electrochemical gradient,
equilibrium potential (Ek) and membrane permeability. Other
factors include temperature, membrane stretching and ligand
binding.
There factors can vary due to ICF and ECF K+ concentrations like
hyperkaliemia, cell excitability etc.
- Nernst equation
Calculates voltage needed to counterbalance diffusion of ions
across the membrane
So basically, calculate equilibrium potential (Eion) through this
equation
Eion is a point at which an ion can maintain equal and opposite
forces
,\
Ek is around -80 mV
Ena is around +60 mV
But Vm is close to Ek at RMP, why?
This is due to the selective free permeability of nerve cell to K+
But the actual membrane potential of the cell is an average of
Eion of K+, Na+, Cl- and Ca2+. This is quantified by Goldmann
Equation, where each ion individually contributes to membrane
potential. This is ALSO A REASON why membrane potential is
closer to K+ than Na+ (and leak channels and the ATPase pump),
along with selective permeability and this also means no ion is in
true equilibrium
- RMP
Always negative inside the cell
Relatively stable
Major determinant is K+ efflux through K+ ion channels
Any channel that can transfer ions across the channel can affect
membrane potential
The differential selective permeability also matters (driving force
for Na+ is large and much higher driving force compared to K+
RMP for excitable cells is -60 to -90 mV RMP and -10 mV RMP for
non-excitable cells
- ECF
Regulated in a narrow range, sensitive to K+ range of 3.5-5.5
mmol/L
, 2 states:
- Note- if membrane was only permeable to K+, Vm would be -80
approx., which would mean Vm = Ek, membrane super sensitive to
changes in ECF K+ con.
Lecture 3 – action potential
- RMP
At rest
-70 mV
All permeable ions contribute to it
Membrane potential close to equilibrium potential of an ion with
highest permeability, i.e. K+
Maintained by Na+K+ ATPase for maintaining gradients
Electrogenic
- Neural response to electrical activation
1. Upon activation due to stimuli, voltage gated Na+ channels
open up, INFLUX of Na+ occurs. These are called VGNaC,
rapid influx, faster than Na+K+ ATPase
2. Influx of Na+ causes neurons to become more +ve or less -ve
than usual. This is called depolarization (more +ve)
3. Depolarization brings neurons closer to 0 than compared to tis
RMP which is -70 mV and even positive if stimulus is strong
enough
4. So, the level of depolarization is proportional to strength of
stimulus applied
5. If membrane is depolarized enough, the threshold point is hit
to generate an all-or-nothing event, approx. -55 mV. This point
is described as the point where Na+ entry is greater than K+
exit/efflux and characterized by VGNaC openings.