G-Protein

ligand binds to its G-Protein 1. Enzyme (active/inactive)

Receptor (G-protein
coupled receptor) 2nd messenger 2. Channel (open/closed)

Definition:
Proteins which are coupled to
receptors, Called G-Proteins because
the use GTP instead of ATP

Main Function: changing the activity

of an effector: Channels or Enzymes
Structure:
3 subunits; (α, β and ϒ).
α is the active subunit

Forms:
Active (on) >>> α bound to GTP
Inactive (off) >>> α bound to GDP

Receptor:
G-protein coupled receptor

 Example on G protein activating a channel

Example:
- Chemical gated K+ channels
- Chemical gated Na+ channels
  Example on G protein activating an enzyme

Ligand Binds with a receptor,

G-protein coupled receptor
(GPCR)

G-Protein becomes Activated

by consumption of GTP

The activated G-Protein

activates another enzyme
Adenylate Cyclase
Phospholipase C Activated
Activated
PIP2 ATP

PIP2 is converted to ATP is concverted

DAC,IP3 to cAMP

DAC cAMP
+ IP3
High [IP3] High [cAMP]
intracellularly intracellularly

IP3 binds to Ca+ Protein Kinase A

channels on ER

Change in cell activity. Phosphorylated

Ca+ release for ER protein

.
 MEMBRANE POTENTIAL

Excitable cells can generate membrane potentials (voltages).

Examples: neurons, muscle cells (skeletal, cardiac, and
smooth).

Membrane Potential (Em): Difference in electric potential

between the intracellular and the extracellular of a cell, so
the membrane is polarized (-40 to -90 mV).

Note = membrane potential is (- or +) we are comparing the inside with

Plasma membrane act as
outside of the cell.
For example:
 Resistor: it has high resistance for
 if the membrane potential is -10 mV this means that’s its negative
the flow of ions (by channels)
inside comparing with outside of the cell
 Capacitor: it separates the charges
 If the membrane potential is +10 mV this means that’s it is positive
inside comparing with outside of the cell

Equilibrium potential for an ion

Nernst equation:
• EK+ = (-94 mV)
• ENa+ = (+61 mV)
• ECl- = (-70 mV)
E =equilibrium potential for a
Measured by Nernst equation for single ion. univalent ion
Co = concentration outside the cell
Ci = concentration inside the cell.

what do we mean by Equilibrium potential?

Point where the Net diffusion of ion is zero, no movement

(ionic current) inside or outside the cell, why?
Electrical force (electrical gradient) is equal to chemical force
(chemical gradient)

Equilibrium
The concentration The electrical gradient.
gradient (chemical force)
potential (electrical force)
Net diffusion
ΔGconc is zero ΔGvolt
ΔGconc = ΔGvolt
Resting membrane potential
membrane potential for a cell under resting conditions when no stimulus
is involved. For neurons the recorded resting membrane potential is
about (– 90 mV).

In neurons, RMP is around -90mV.

This depends on 3 factors:
1- Ions’ (Na+ & K+) concentration gradient & Equilibrium Potential
by Goldman equation is -86 mv
2- Na+/K+ Pump -4 mV
Goldman-Hodgkin-Katz equation.
3- Ions’ permeability

Q: RMP is closer to the Eq of K+ than Na+?

because of the higher permeability of membrane for K+ than for Na+ (100  Equilibrium potential
times more).  Permeability

Resting
membrane
EK+ ENa+
potential
-94 +61
-90

1. The resting potential of a nerve membrane is primarily dependent on the concentration gradient of
a. Potassium b. Sodium c. Calcium d. Chloride e. Bicarbonate

2. Excitable tissues have different resting membrane potential, for example in nervous cells -90 mV cardiac
muscle cells it could be -60 mV, in smooth muscle cells -50, in skeletal muscle cells – 70, Why?

It is according to the permeability to Na+, K+, and the presence of the Na+ - K+ pump.

3. muscle cell has an intracellular [Na+] of 14 Mm and extracellular [Na+] of 140 Mm. if 2.3 RT/F = 60 mv, what
would the membrane potential be if the muscle cell membrane were permeable only to Na+
a. -80 mv
b. -60 mv
c. 0 mv
d. +60 mv
e. +80 mv
 4. if we have Cl- channels open over the resting membrane potential for Cl- , what is the effect on membrane
potential?
When we reach the equilibrium potential for Cl- then channels open, and the net movement of Cl- is zero, so
there is no affect

5. how we can measure the flow (current) of ions crossing the membrane?
Patch clamp

6. Using Patch Clamp technique, if we set the potential across the

membrane at -94 mV, what will be the ionic current for K+?

Action Potential
Na+ K+
Concentration Higher extracellular Higher Intracellular
(Tends to go intracellularly if channels (Tends to go extracellularly if channels open)
open)
Increase in permeability (conductance) of a certain ion (by opening it’s channel) will result in membrane
potential getting closer to the Eq of that ion
Change when  Na+ Influx (From ECF to ICF)  K+ efflux (From ICF to ECF)
specific channels  Intracellular comes more POSITIVE  Intracellular becomes more NEGATIVE
open (increase in  Em gets closer to that of Na+  Em gets closer to that of K+ (increased)
permeability) (decreased)- closer to +61mV – closer to -94mV
 DEPOLARIZATION  HYPERPOLARIZATION/REPOLARIZATI
ON
 Chemical Gated Channels (CGC) Voltage Gated Channels (VGC)
Trigger Ligand binding to its receptor Voltage/potential change
Ions involved Na+ only Na+ (fast) & K+ (slow/delayed opening)

Stages Depolarization Depolarization (Na+ channels opened) &

involved Repolarization (K+ channels opened, Na+
channels closed)