Isoflurane inhibits transmitter release and the presynaptic action potential.
نویسندگان
چکیده
BACKGROUND Isoflurane inhibits the excitatory postsynaptic current (EPSC) at many synapses. Accumulated evidence suggests the involvement of a presynaptic mechanism. However, the extent of the presynaptic contribution has not been quantitatively studied. Furthermore, the mechanism underlying the presynaptic contribution remains unclear. METHODS To estimate the presynaptic contribution, the authors compared the effects of isoflurane on the presynaptic capacitance jump, which is proportional to vesicle release, and the postsynaptic glutamate receptor-mediated EPSC at a calyx-type synapse in rat brainstem. The authors determined whether isoflurane affects the waveform of the action potential recorded from nerve terminals. By studying the relation between the EPSC and the presynaptic action potential at the same synapse, the authors determined whether isoflurane inhibits the EPSC by decreasing the presynaptic action potential. RESULTS Isoflurane at 0.35-1.05 mM reduced the EPSC and the presynaptic capacitance jump to a similar degree without affecting the miniature EPSC (an indicator of quantal size), suggesting that isoflurane inhibits the EPSC predominantly by reducing glutamate release. Isoflurane reduced the presynaptic action potential by approximately 3-8%. The EPSC was proportional to the presynaptic action potential amplitude raised to a power of 10.2. Based on this relation, inhibition of the presynaptic action potential contributed to 62-78% of isoflurane-induced inhibition of the EPSC. CONCLUSIONS Isoflurane inhibits the EPSC predominantly by inhibition of transmitter release. Isoflurane reduces the presynaptic action potential amplitude, which may contribute significantly to its inhibitory effect on the EPSC.
منابع مشابه
Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse.
Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers neurotransmitter release. Action potential duration plays a determinant role in the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+ influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The effect of action potential duration on Ca2+ influx and transmitter release was investi...
متن کاملEffects of isoflurane and propofol on glutamate and GABA transporters in isolated cortical nerve terminals.
BACKGROUND Depression of glutamate-mediated excitatory transmission and potentiation of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission appear to be primary mechanisms by which general anesthetics produce anesthesia. Since effects on transmitter transport have been implicated in anesthetic actions, the authors examined the sensitivity of presynaptic glutamate and GABA transporte...
متن کاملCan presynaptic depolarization release transmitter without calcium influx?
Recent experimental evidence suggesting that presynaptic depolarization can evoke transmitter release without calcium influx has been re-examined. The presynaptic terminal of the squid giant synapse can be depolarized by variable amounts while recording presynaptic calcium current under voltage clamp and postsynaptic responses. Small depolarizations open few calcium channels with large single c...
متن کاملPresynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane.
BACKGROUND Presynaptic effects of general anaesthetics are not well characterized. We tested the hypothesis that isoflurane exhibits transmitter-specific effects on neurotransmitter release from neurochemically and functionally distinct isolated mammalian nerve terminals. METHODS Nerve terminals from adult male rat brain were prelabelled with [(3)H]glutamate and [(14)C]GABA (cerebral cortex),...
متن کاملPresynaptic Ca Influx at the Inhibitor of the Crayfish Neuromuscular Junction: A Photometric Study at a High Time Resolution
Vyshedskiy, Andrey and Jen-Wei Lin. Presynaptic Ca influx at the inhibitor of the crayfish neuromuscular junction: a photometric study at a high time resolution. J. Neurophysiol. 83: 552–562, 2000. Presynaptic calcium influx at the inhibitor of the crayfish neuromuscular junction was investigated by measuring fluorescence transients generated by calcium-sensitive dyes. This approach allowed us ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Anesthesiology
دوره 100 3 شماره
صفحات -
تاریخ انتشار 2004