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

Lynch, Carl; Miao, Ning; Nagao, Kaoru; Pancrazio, Joseph J.

doi:10.24015/japm.2017.0016

Cited by 1 publication

(1 citation statement)

References 44 publications

(59 reference statements)

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“…However, our results indicate that differential presynaptic VGCC subtype expression does not contribute to differences in sensitivity of SV exocytosis to isoflurane in hippocampal neurones. These results are consistent with previous electrophysiological studies showing that isoflurane inhibits P/Q-and N-type Ca 2þ currents to a similar extent in rat hippocampal pyramidal neurones, 9 cultured cerebellar granule neurones, 10 and Xenopus oocytes heterologously expressing mammalian N-or P/Q-type channels. 37 In contrast, isoflurane was reported to inhibit N-type currents to a greater extent than P/Q-type currents in rat dorsal root ganglion neurones.…”

Section: Discussionsupporting

confidence: 93%

Role of specific presynaptic calcium channel subtypes in isoflurane inhibition of synaptic vesicle exocytosis in rat hippocampal neurones

Koyanagi

Torturo

Cook

et al. 2019

British Journal of Anaesthesia

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Background: P/Q-and N-type voltage-gated calcium channels (VGCC) are the principal subtypes mediating synaptic vesicle (SV) exocytosis. Both the degree of isoflurane inhibition of SV exocytosis and VGCC subtype expression vary between brain regions and neurotransmitter phenotype. We hypothesised that differences in VGCC subtype expression contribute to synapse-selective presynaptic effects of isoflurane. Methods: We used quantitative live-cell imaging to measure exocytosis in cultured rat hippocampal neurones after transfection of the fluorescent biosensor vGlut1-pHluorin. Selective inhibitors of P/Q-and N-type VGCCs were used to isolate subtype-specific effects of isoflurane. Results: Inhibition of N-type channels by 1 mM u-conotoxin GVIA reduced SV exocytosis to 81±5% of control (n¼10). Residual exocytosis mediated by P/Q-type channels was further inhibited by isoflurane to 42±4% of control (n¼10). The P/ Q-type channel inhibitor u-agatoxin IVA at 0.4 mM inhibited SV exocytosis to 29±3% of control (n¼10). Residual exocytosis mediated by N-type channels was further inhibited by isoflurane to 17±3% of control (n¼10). Analysis of isoflurane effects at the level of individual boutons revealed no difference in sensitivity to isoflurane between P/Q-or N-type channelmediated SV exocytosis (P¼0.35). There was no correlation between the effect of agatoxin (P¼0.91) or conotoxin (P¼0.15) and the effect of isoflurane on exocytosis. Conclusions: Sensitivity of SV exocytosis to isoflurane in rat hippocampal neurones is independent of the specific VGCC subtype coupled to exocytosis. The differential sensitivity of VGCC subtypes to isoflurane does not explain the observed neurotransmitter-selective effects of isoflurane in hippocampus.

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Section: Discussionsupporting

confidence: 93%