Desensitization and resensitization kinetics of glutamate receptor channels from Drosophila larval muscle

Outside-out patches from wild-type Drosophila larval muscle were exposed to L-glutamate (glu) using a piezo-driven application system. Glu receptor channels opened and desensitized in response to rapid applications of 10 mM glu. Desensitization was fitted with an exponential function with a mean time constant of desensitization (tau d) of 15 ms in response to 10 mM glu. The tau d was concentration dependent and decreased to 6 ms (on average) with 0.7 mM glu and increased again to 12 ms (on average) in response to 0.5 mM glu. Desensitization in response to longer applications of glu was almost complete, but surprisingly, even a 1-ms pulse of 3 mM glu produced about 30% desensitization. In the presence of low glu concentrations, the response to a pulse was reduced and was about halved by preequilibration with 30 microM glu. Recovery from desensitization was not concentration dependent and was fitted with an exponential function with a mean time constant of 150 ms. During recovery the channels rarely opened. Kinetic schemes were fitted to these results, and a circular reaction scheme was found to fit the data best. An important feature of the scheme is desensitization from a lower ligated closed state. This allows substantial desensitization of synaptic receptor channels in response to quantal release of transmitter, in part without opening of the channels. Desensitization reduces the probability of the channels opening in response to a subsequent release for a period of time determined by the rate of recovery from desensitization and might serve as a form of molecular short-term memory.