Lec 9

2. Depolarization also leads to slower inactivation of g_Na so soon after
the conductance is turned on it turns itself off and the Na conductance decreases again to its resting level.  This is the major reason why the action potential is self-limiting

Depolarization also leads to a slow increase in g_K , so the outward K
current increases and hyperpolarizes the membrane. g_K is still on after g
Na has turned off, so at this point V_m is closer to E_K than before the
action potential started.  This is called the after-hyperpolarization.
After the hyperpolarization, g_K turns off (because of the hyperpolarization,
not because of inactivation) and g_K returns to the resting state.

1. If we substitute choline (an impermeant monovalent cation) for Na⁺,
there is no action potential. (This suggests that Na⁺ is important) 

              (2) We can measure the movement of Na⁺  and  K⁺ during action potentials using radioisotopes (²⁴Na⁺ and ⁴²K⁺). For sodium, we measure the accumulation of  ²⁴Na ⁺  in a neuron following a given number of action
potentials. For potassium, we preload the cell with ⁴²K⁺ and measure the
efflux. Using this method we calculate that for a single action potential, about 3 x 10^-12 moles per square cm of Na⁺ enters the cell and the same amount of
K⁺  leaves the cell.

The action potential occurs because the movement of  Na⁺  and  K⁺
changes the charge on the membrane, NOT because the ionic concentration in
the cytoplasm changes.
*Na⁺ and K⁺ flow mean Na⁺ and K⁺ current, and these currents flow as a result of increases in g_Na and g_K brought about by the depolarization. 

To sort this out, Cole, Hodgkin and Huxley used a VOLTAGE
CLAMP to keep the voltage across the membrane constant so that for each set
voltage they could measure the currents as a function of time, without letting the current flow due to the conductance change affect the membrane potential, as it does during the actual action potential.  With the
voltage constant, the current records enable you to calculate the way the
conductances change with time.  

1. step Vm to a new value and hold it there; this
induces a change in the conductance of the membrane -- we measure the
membrane current as a function of time after the voltage step. This allows
the measurement of conductance as a function of time.  Then repeat the experiment by stepping to a different V_m.  This will lead to a description of the properties of the channels, and at the end we'll see if this describes the action potential.

If there is a voltage between the input terminals A and B on the feedback
amplifier, the amplifier sends a current across resistor C until A and B are
at the same voltage. This is the same as the membrane current because the electronics supplies an equal and opposite current to keep the voltage constant.  Voltage command
at A (from V_ref) can set and hold Vm.

where early peak current crosses V
axis. If we vary the concentration of sodium outside the cell, we change
this reversal potential (V_rev), so we conclude that the early current is
carried by sodium.

      The voltage clamp measures the total membrane current.  It is possible to separate this into individual Na and K currents by analyzing the graphs, and that is what Hodgkin and Huxley originally did.  However, nowadays there are selective toxins available that block the sodium current or the potassium current. Can block the sodium current with tetrodotoxin
(TTX).  This lets us see the 'pure' late (K⁺) current.

      Now, having isolated the Na and K currents, we can calculate the
conductances from
                I_Na = g_Na (V_m - E_Na)

                I_K = g_K (V_m - E_K)
  Note that the conductance depends on voltage  -- this is a
voltage-dependent resistance - NOT OHMIC.