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Action Potential in a Neuron. Rricketson 11.16.2012
                              Copyright © 2012 Seaspine. All rights reserved.
                                                                                1
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.




                                                                    2
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+
                                                                   3
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+

                                                                                 4
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+
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)-




                                                             6
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

                                                         7
VOLTAGE GATED SODIUM CHANNEL (NAV)

Interactive walk-through of the Action Potential.




                                                    8
THANK YOU




            9

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Action potential in a neuron part 3 voltage gated sodium channel

  • 1. Action Potential in a Neuron. Rricketson 11.16.2012 Copyright © 2012 Seaspine. All rights reserved. 1
  • 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. 2
  • 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+ 3
  • 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+ 4
  • 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)- 6
  • 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 7
  • 8. VOLTAGE GATED SODIUM CHANNEL (NAV) Interactive walk-through of the Action Potential. 8