The loop diuretic furosemide is known to have anticonvulsant effects, believed to be exerted through blockade of glial Na-K-Cl cotransport causing altered volume regulation in brain tissue. The possibility that direct effects of furosemide on neuronal properties could also be involved is supported by previous observations, but such effects have not been thoroughly investigated. In the present study we show that furosemide has two opposing effects on stimulus-induced postsynaptic excitation in the non-epileptic rat hippocampal slice: i) an enhancement of e-s coupling, which depended on intact GABAA transmission and was partially mimicked by selective blockade of K-Cl cotransport, and ii) a decrement of fEPSPs. The balance between these effects varied, depending on the amount of synaptic drive. In addition, the compound action potential (fiber volley) recorded from the stimulated Schaffer collateral axons in stratum radiatum showed a progressive decrease during perfusion of furosemide. This effect was activity-independent, was mimicked by the stilbene derivative DIDS, and could be reproduced on fiber volleys in the alveus. Furosemide also reduced the initial enhancement of the fiber volley observed during trains of high-frequency stimulation (HFS). Hyperosmotic expansion of the extracellular volume, using 30 mM sucrose, indicated that the induction and antagonism of HFS-induced enhancement were independent on signaling via the extracellular space. Furosemide caused an increased decay of paired-pulse induced supranormal axonal excitability, which was antagonized by ZD7288. We conclude that furosemide decreases axonal excitability and prevents HFS-induced hyperexcitability via mechanisms downstream to blockage of anion transport, which could include hyperpolarization of axonal membranes.
- anion transport
- fiber volley
- Copyright © 2016, Journal of Neurophysiology