Publication: Changes in spinal inhibitory networks induced by furosemide in humans
Issued Date
2014-07-01
Resource Type
ISSN
14697793
00223751
00223751
Other identifier(s)
2-s2.0-84903556527
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Physiology. Vol.592, No.13 (2014), 2865-2879
Suggested Citation
Wanalee Klomjai, Alexandra Lackmy-Vallée, Rose Katz, Bernard Bussel, Djamel Bensmail, Jean Charles Lamy, Nicolas Roche Changes in spinal inhibitory networks induced by furosemide in humans. Journal of Physiology. Vol.592, No.13 (2014), 2865-2879. doi:10.1113/jphysiol.2013.265314 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/33248
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Changes in spinal inhibitory networks induced by furosemide in humans
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 KCC2 after spinal cord transection in animals leads to the depolarising (excitatory) action of GABA 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 (40 mg), significantly reduced spinal inhibitory interneuronal activity for at least 70 min from intake 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. © 2014 The Physiological Society.