Glutamate-activated ion currents in photoreceptors: Fluctuation analysis and miniature presynaptic currents.

摘要

I have studied the glutamate-activated current in photoreceptors from the tiger salamander using noise analysis. The results from the noise analysis show that the current is generated by 2*10{dollar}sp4{dollar} glutamate-activated chloride channels. The channels have a unit conductance of 0.7 pS and an open lifetime of 2.4 ms. The channel activation requires the presence of both glutamate and sodium. The single-channel conductance is independent of the concentration of glutamate and sodium. Glutamate and sodium affect only the channel opening rate. {dollar}beta{dollar}-hydroxy-aspartate is shown to be a partial agonist. The single-channel conductance is the same regardless of whether glutamate or {dollar}beta{dollar}-hydroxy-aspartate is the ligand, but the open lifetime of the channel is shortened to 0.8 ms with {dollar}beta{dollar}-Hydroxy-Aspartate as ligand. The results are interpreted in terms of different models of channels and channel/carrier hybrids. The hybrid models are introduced to take into account the unusual sodium dependence and pharmacology of the chloride channel and the reports of glutamate uptake into photoreceptors.; I further show that a single isolated photoreceptor responds to its own vesicular release of glutamate. The glutamate-activated chloride channel is the detector of the vesicular release. This is the first current recording of a presynaptic detection of the quantal release of an endogenous neurotransmitter.; Since the reversal potential for chloride in vivo is more negative than the membrane potential of the cell, activation of the glutamate-activated chloride channel by glutamate release would hyperpolarize the photoreceptor. Vesicular release is calcium dependent, and calcium influx is voltage dependent. Thus, the hyperpolarization would prevent calcium influx and hence prevent further glutamate release. This indicates that the glutamate-activated chloride channel fills a physiological function as part of a negative feedback loop that regulates the amount of released glutamate.