5‐hydroxytryptamine‐mediated increase in glutamate uptake by the leech giant glial cell

Abstract

The clearance of synaptically released glutamate is one of the pivotal functions of glial cells. We have studied the role of 5-hydroxytryptamine (5-HT, 30 microM), a neurotransmitter and neurohormone in the leech central nervous system with a versatile action spectrum, on the efficacy of glial glutamate uptake. The activity of the glutamate uptake carrier in the giant glial cell in isolated ganglia of Hirudo medicinalis was monitored by measuring the membrane current and the change in the intracellular Na(+) concentration (Na(+) (i)) as induced by the glutamate carrier substrate D-aspartate (D-asp, 1 mM). 5-HT increased the D-asp-induced current (EC(50) at 5 microM) and rise in Na(+) (i), an effect which was mimicked by the membrane-permeable cyclic nucleotide analogue dibutyryl-cyclic AMP (db-cAMP). The adenylyl cyclase inhibitor SQ 22,536 and the protein kinase A antagonist Rp-cAMP inhibited the effect of 5-HT. Blocking the G protein in the giant glial cell by injecting GDP-beta-S suppressed the effect of 5-HT, but not the effect of db-cAMP, on the D-asp-induced current. Our results suggest that 5-HT enhances the glial uptake of glutamate via cAMP- and PKA-mediated pathway.

Physiology of Astroglia

“…They express multiple types of neurotransmitter receptors including ionotropic glutamate, acetylcholine, and serotonin receptors as well as metabotropic receptors to glutamate, serotonin, myomodulin, and possibly P 2Y -like purinoceptors and A 1 -like adenosine receptors (403,1166). Giant glial cells participate in homeostatic responses, such as regulation of pH involving several plasmalemmal Na ϩ -HCO 3 Ϫ cotransporter, Na ϩ -H ϩ and Cl Ϫ -HCO 3 Ϫ exchangers (399,404,405), as well as in regulation of neurotransmitters turnover through Na ϩ -dependent glutamate and Na ϩ -dependent choline transporters (407,705,1898). Giant glial cells respond to neuronal activity and to evoked behaviors by changes in membrane potential (400) as well as by generation of cytosolic Ca 2ϩ signals that occur in both somata and processes, often in compartmentalised manner (1004).…”

Stratification of astrocytes in healthy and diseased brain

“…Packet glia regulate K + homeostasis around neuronal somata , whereas giant glial cells control ion homeostasis in the neuropil, being particularly important for regulation of pH (by plasmalemmal Na + ‐ co‐transporter, Na + ‐H + and Cl – ‐ exchangers). Furthermore giant glial cells remove extracellular glutamate and choline through dedicated Na + ‐dependent plasmalemmal transporters .…”

Direct Effects of Riluzole on 5-Hydroxytryptamine (5-HT)3 Receptor–Activated Ion Currents in NCB-20 Neuroblastoma Cells

“…As GDP-β-S or PTX are generally used to block G-protein-mediated intracellular signaling mechanisms (25,26), if riluzole inhibits 5-HT 3 -receptor function through the G-proteinrelated intracellular mechanism, both of these drugs should block the effect of riluzole. However, neither GDP-β-S nor PTX treatment within the pipette solution or culture medium blocked the inhibitory effect of riluzole (Fig.…”