A potential role for astrocytes in mediating the antiepileptic actions of furosemide in vitro

• Published in: Neuroscience Vol. 128; no. 3; pp. 655 - 663
• Main Authors: Barbaro, N.M., Takahashi, D.K., Baraban, S.C.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2004; Elsevier
• Subjects: 4-Aminopyridine - pharmacology; Action Potentials - drug effects; Action Potentials - physiology; Animals; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; astrocyte; Astrocytes - drug effects; Astrocytes - physiology; Barium - pharmacology; Biological and medical sciences; Cesium - pharmacology; epilepsy; Epilepsy - drug therapy; Epilepsy - metabolism; Epilepsy - physiopathology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Fundamental and applied biological sciences. Psychology; Furosemide - pharmacology; hippocampus; Hippocampus - drug effects; Hippocampus - physiology; Medical sciences; Mice; Neural Pathways - drug effects; Neural Pathways - physiology; Neurons - drug effects; Neurons - physiology; Neuropharmacology; non-synaptic; Organ Culture Techniques; patch-clamp; Patch-Clamp Techniques; Pharmacology. Drug treatments; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels - physiology; seizure; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vertebrates: nervous system and sense organs; epilepsy; AED; Rs; seizure; hippocampus; patch-clamp; ACSF; nACSF; IR-DIC; 4-AP; non-synaptic; EPSC; sACSF; K IR; astrocyte; Nervous system diseases; Neuroglia; Epilepsy; Central nervous system; Electrophysiology; Patch clamp method; Anticonvulsant; Astrocyte; In vitro; Furosemide; Cerebral disorder; Central nervous system disease; Hippocampus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2004.07.007

Epileptic seizures are characterized by abnormal electrical discharge. In previous studies we established a powerful antiepileptic action for a commonly used diuretic (furosemide). However, it remains unclear precisely how furosemide terminates abnormal electrical discharges. To address this issue, we performed in vitro experiments to examine conditions where furosemide exerts antiepileptic activity and patch-clamp studies to analyze the effect of furosemide on neuronal membrane properties, synaptic function and inward potassium current. Furosemide was not found to alter synaptic field responses, excitatory postsynaptic currents or intrinsic membrane properties of principal hippocampal neurons. Our in vitro studies indicate that furosemide does not abolish spontaneous epileptiform bursting during co-application of Ba 2+ or Cs + ions (to block inwardly rectifying potassium channels). Our patch-clamp data indicate that furosemide enhances the function of astrocytic, but not neuronal, inward potassium channels and that this modulation may be required for its antiepileptic activity. Although a variety of antiepileptic drugs are already available, none of these compounds selectively target astrocytes while preserving synaptic/neuronal function. Thus, furosemide-mediated modulation of inward potassium current (on astrocytes) represents a new target for control of abnormal electrical discharge in the CNS.