2. THE MEMBRANE POTENTIAL-THE NA-K ATPASE PUMP
The Na+/K+-ATPase pump helps maintain membrane
potential.
Moves 3 sodium ions out and 2 potassium ions in, (removes 1 +
charge) against concentration gradient
Responsible for up to 2/3 of the neuron’s energy expenditure.
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3. THE MEMBRANE POTENTIAL-THE NA-K ATPASE PUMP
Mechanism (PDB ID 2B8E, 2ZKE
biological assembly)
K+
K+
Unphosphorylated form binds 3
intracellular Na+ ions while
binding ATP
Hydrolysis of ATP ADP +
Phosphorylation of the pump at
a highly conserved Aspartate
residue; ADP + Pi.
Phosphorylated form has a low
affinity for Na+ Release
Pump binds 2 extracellular K+
ions Dephosphorylation.
Dephosphorylation high affinity
for Na+ ions. K+ (2) Released
Na+
K+ ions are transported into the
cell. Na+
Na+
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4. THE MEMBRANE POTENTIAL-THE POTASSIUM CHANNEL
Mechanism (PDB ID 2EKW,
biological assembly)
A neuron is permeable to K+
Allows K+ to move from high [K+]o =5 mmol
concentration in the cytoplasm to low
K+
concentration in the extracellular
environment
K+
Potassium diffuses out of the cell
from its higher to lower
concentration (chemical force).
The Electrical potential or Vm= -90 mV
electrical force pulls K+ in to the
cell. At equilibrium Vm= -90 mV
The forces are equal and opposite K+
[K+]i =150 mmo
K+ K+
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5. THE RESTING POTENTIAL
Resting potential (EK )refers to
the difference between the
voltage inside and outside the
neuron when not propagating an
Cl-
impulse. The resting potential of K+
the average neuron is around -70
Na+
mVT The inside of the cell is 70 Na+
mV less than the outside of the Na+
cell. Na+
K+
Na+
K+
K+
Cl-
K+
6. VOLTAGE GATED SODIUM CHANNEL (NAV)
Voltage Gated Na Channel
(PDB ID 2EKW, biological assembly)
6 helical segments. S1-S6
S4-Voltage Sensor 4 Arg + charged
residues. Depolarization phase of AP
Conformational change via linker S4-S5
“P” loops between S5 and S6 form pore
- charged Glu and Asp line pore and attract Na+ ions.
Inactivaton Gate (S5 and S6) closes pore
(repolarization)
Three states:
Deactivated (closed)
Activated (open)
Inactivated (closed)-
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7. GENERATING THE ACTION POTENTIAL
Generated in axon hillock and Nodes of
Ranvier of neurons by special types of
voltage gated ion channels (Na+, Ca++)
embedded in a cell's plasma membrane
Threshold is –55 mV for Na+ channel
recruitment
Amplitude is independent of the
amount of current (all or nothing)
Rising Phase:
• Rapid influx of Na+ causes a:
• Depolarization of membrane
potential
• Inactivation of Na+ channels (ENa≈
+55 mV)
Falling Phase:
• K+ channel activation
(repolarization)
Afterhyperpolarization
• K+ channels slow to close
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8. VOLTAGE GATED SODIUM CHANNEL (NAV)
Interactive walk-through of the Action Potential.
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