A Postsynaptic Excitatory Amino Acid Transporter with Chloride Conductance Functionally Regulated by Neuronal Activity in Cerebellar Purkinje Cells

Abstract

Excitatory amino acid (EAA) neurotransmitters induce postsynaptic depolarization by activating receptor-mediated cation conductances, a process known to underlie changes in synaptic efficacy. Using a patch-clamp method, we demonstrate here an EAA-dependent postsynaptic anion conductance mediated by EAA transporters present on cerebellar Purkinje cell bodies and dendrites in culture. This transporter-mediated current was modulated by neuronal activity: it exhibited facilitation for Ͼ20 min after transient depolarization accompanied by Ca 2ϩ influx.Evidence is presented suggesting that the transporter facilitation is mediated by arachidonate release after Ca 2ϩ -dependent activation of phospholipase A 2 , which exists in Purkinje cells. This postsynaptic reuptake system may represent a novel modulatory mechanism of synaptic transmission as well as prevent neuronal excitotoxicity.

Arachidonic Acid Activates a Proton Current in the Rat Glutamate Transporter EAAT4

“…Whether exogenously applied or generated by depolarization, arachidonic acid increased the amplitude of glutamate transporter-mediated currents in rat Purkinje cells (5). The amplitude of the increase seen in Purkinje cells was similar to that reported here with the exogenously expressed EAAT4.…”

“…Transporter-mediated currents in Purkinje neurons are increased more than 3-fold by arachidonic acid, a second messenger that is liberated following depolarization-induced Ca 2؉ activation of phospholipase A 2 (5). In this study we demonstrate that application of arachidonic acid to oocytes expressing rat EAAT4 increased glutamate-induced currents to a similar extent.…”

“…Arachidonic acid is liberated by activation of phospholipase A 2 during neuronal activity (5,36), and it can modulate activitydependent changes in synaptic strength in Purkinje cells (18). Whether exogenously applied or generated by depolarization, arachidonic acid increased the amplitude of glutamate transporter-mediated currents in rat Purkinje cells (5).…”

“…Because arachidonate is released during synaptic activity and can modulate synaptic transmission (17,18), understanding its effects on various glutamate transporter subtypes is important. Recently, Kataoka et al reported an activity-dependent enhancement of glutamate transporter currents in rat cerebellar Purkinje neurons that was mediated by arachidonate (5). The present study was designed to examine the mechanism of the effects of arachidonate on the cloned rat EAAT4 transporter, which is expressed at high levels in Purkinje neurons.…”

Glial Glutamate Transporters Limit Spillover Activation of Presynaptic NMDA Receptors and Influence Synaptic Inhibition of Purkinje Neurons

“…The activity and expression of neuronal and glial glutamate transporters are subject to regulation by glutamate itself and by several endogenous substances released by excitatory granule cells or Purkinje neurons in an activity-dependent manner (Kataoka et al, 1997;Swanson and Duan, 1999), suggesting that glutamate transporters dynamically regulate GABA release onto Purkinje neurons. Such a dynamic mechanism may also apply in other brain areas, such as the hippocampus, in which presynaptic kainate-receptor activation modulates GABA release (Kullmann, 2001).…”