Publication: Changes in spinal inhibitory networks induced by furosemide in humans
Issued Date
2014
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eng
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Mahidol University
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The Physiological Society
Bibliographic Citation
The Journal of Physiology. Vol.592, No.13 (2014), 2865-2879
Suggested Citation
Wanalee Klomjai, Lackmy-Vall´ee, Alexandra, Katz, Rose, Bussel, Bernard, Bensmail, Djamel, Lamy, Jean-Charles, Roche, Nicolas Changes in spinal inhibitory networks induced by furosemide in humans. The Journal of Physiology. Vol.592, No.13 (2014), 2865-2879. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/10989
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Title
Changes in spinal inhibitory networks induced by furosemide in humans
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Abstract
Abstract During neural development in animals, GABAergic and glycinergic neurons are first
excitatory, and then become inhibitory in the mature state. This developmental shift is due mainly
to strong expression of the cation-chloride K–Cl cotransporter 2 (KCC2) and down-regulation of
Na–K–Cl cotransporter 1 (NKCC1) during maturation. The down-regulation of co-transporter
KCC2after spinal cord transection inanimals leads to the depolarising (excitatory) action ofGABA
and glycine and thus results in a reduction of inhibitory synaptic efficiency. Furosemide, a loop
diuretic, has been shown to selectively and reversibly block inhibitory postsynaptic potentials
without affecting excitatory postsynaptic potentials in animal spinal neurons. Moreover, this
diuretic has been also demonstrated to block the cation-chloride co-transporters. Here, we used
furosemide to demonstrate changes in spinal inhibitory networks in healthy human subjects.
Non-invasive electrophysiological techniques were used to assess presynaptic inhibition, postsynaptic
inhibition and the efficacy of synaptic transmission between muscle afferent terminals
and soleus motoneurons in the spinal cord. Orally administered furosemide, at doses commonly
used in the clinic (40mg), significantly reduced spinal inhibitory interneuronal activity for at least
70 min fromintake compared to control experiments in the same subjects while no changes were
observed in the efficacy of synaptic transmission between muscle afferent terminals and soleus
motoneurons. The reduction of inhibition was dose-dependent. Our results provide indirect
evidence that reversible changes in the cation-chloride transport system induce modulations of
inhibitory neuronal activity at spinal cord level in humans.