Activation, Desensitization and return from Desensitization of the dAMPA receptor

Run this simulation by typing:                       spike desens.hoc -

Activation of the dAMPA receptor is demonstrated by giving brief pulses of glutamate in a single compartment model. Try incrementing the duration of the glutamate pulse from 0.25ms. to 3.0 ms. in 0.25 ms. steps by pressing run in the ‘Family Function Panel’

The voltage of the compartment is clamped at a constant -65mV.(not illustrated) and we observe the current necessary to maintain this voltage in the face of a conductance change caused by application of glutamate to the dAMA receptor

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We generate a family of curves representing the current evoked by pulses of Glutamate with increasing durations

What can we say about the amplitude of the current as glutamate duration increases?

Please THINK about this before turning the page.....You’ll be glad you did. 

The above curves demonstrate three aspects of receptor physiology. Activation, Deactivation and Desensitisation. The response grows with increasing duration of Glutamate application until about 1.25 ms. A very brief pulse of transmitter exhibits less than the maximal amount of current; this phenomena is refered to as deactivation. The receptor is said to deactivate as Glutamate is released from its bound state.

With continued application of transmitter the receptor activates to a peak and then reduces in amplitude. The receptor is becoming desensitized to the presence of the transmitter. After a certain amount of time the receptor fully desensitizes and no current is evoked.

Continuing to increase the duration of Glutamate application leads to complete desensitization of receptor response.

Return from desensitisation

After a receptor is desensitized, there is a refractory period where a subsequent application of transmitter has a diminished effect on opening the receptor pore. To demonstrate this, change the ‘T stop’ variable in the ‘Run Control’ panel to 450 ms. Close the Family Panel, and use the ‘Init & Run’ button in the ‘Run Control’ Panel to start the simulation. Two pulses of Glutamate are presented. Manipulate when the second pulse is presented with the ‘Ramp_Delay’ and ‘Ramp_Off’ parameters in the Glutamate panel, keeping the difference between the two parameters a constant 1ms.

 Describe the recovery from desensitisation.

 Determine when a complete return from desensitization occurs.

    Don’t turn the page until you have done the simulation!!

The recovery from desensitization is roughly exponential and full recovery occurs after 400ms.

Try lengthening the duration of the first Glutamate pulse to 10 ms and repeat the simulations.

How does this compare to the previous simulation?