Volatile Anesthetics Depress Calcium sup 2+ Transients and Glutamate Release in Isolated Cerebral Synaptosomes

Abstract

In this setting, isoflurane, enflurane, and halothane decrease [Ca2+]i in a manner consistent with inhibition of Ca2+ entry, possibly by specific voltage-gated neuronal Ca2+ channels. This decrease in [Ca2+]i is sufficient to account for all or most of the associated decrease in glutamate release.

Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane

“…37 Inhibition of NE release evoked by 4AP-induced depolarization required higher isoflurane concentrations comparable with those that inhibit 4AP-evoked glutamate release from rat 9 and mouse 38 cortical nerve terminals. These less potent effects of isoflurane on depolarization-evoked transmitter release involve effects on presynaptic voltage-gated Na þ channels, 39 Ca 2þ channels, 40 and/or TREK-1 channels. 41 Taken together, these findings indicate that both ligand-gated and voltage-gated ion channels are presynaptic targets for dose-dependent transmitter-selective effects of IAs on transmitter release from mammalian nerve terminals.…”

Concentration‐dependent isoflurane effects on depolarization‐evoked glutamate and GABA outflows from mouse brain slices

“…General anaesthetics have been shown to decrease the depolarization-or anoxia-evoked release of glutamate, a major excitatory amino acid in the central nervous system (CNS) (Bickler et al, 1995;Eilers & Bickler, 1996;Liachenko et al, 1998;Miao et al, 1995;Patel et al, 1995;Schlame & Hemmings, 1995). A less predictable behaviour in response to anaesthetics has been found for the inhibitory neurotransmitter, g-aminobutyric acid (GABA).…”

Volatile Anesthetic Depression of Ca2+ Entry Into and Glutamate Release from Cultured Cerebellar Granule Neurons

“…At clinical concentrations and physiologic temperatures, VAs cause parallel and dose-dependent reductions in Ca 2 + transients and glutamate release from isolated cerebral synaptosomes induced depolarization with 30 mM K + (8). These decreases are similar to those seen with reductions in external Ca 2 + and consistent with VA mediated inhibition of Ca 2 + entry via VGCCs (8). However, inhibition of Na channels also decrease neurotrans-mitter release have raised the possibility that VAs primarily prevent the Na channel-mediated depolarization that opens VGCCs (9)(10)(11).…”

“…In adrenally-derived PC12 cells, VAs inhibited the K + -depolarization rise in intracellular Ca 2 + due to influx via L-and N-type voltage-gated Ca channels (VGCCs) (7). At clinical concentrations and physiologic temperatures, VAs cause parallel and dose-dependent reductions in Ca 2 + transients and glutamate release from isolated cerebral synaptosomes induced depolarization with 30 mM K + (8). These decreases are similar to those seen with reductions in external Ca 2 + and consistent with VA mediated inhibition of Ca 2 + entry via VGCCs (8).…”