The contribution of an impaired astrocytic K^+ regulation system to epileptic neuronal hyperexcitability has been increasingly recognized in the last decade.A defective K^+ regulation leads to an elevated extracellula...The contribution of an impaired astrocytic K^+ regulation system to epileptic neuronal hyperexcitability has been increasingly recognized in the last decade.A defective K^+ regulation leads to an elevated extracellular K^+ concentration([K^+]o).When[K^+]o reaches peaks of 10-12 mM,it is strongly associated with seizure initiation during hypersynchronous neuronal activities.On the other hand,reactive astrocytes during a seizure attack restrict influx of K^+ across the membrane both passively and actively.In addition to decreased K^+ buffering,aberrant Ca^2+ signaling and declined glutamate transport have also been observed in astrogliosis in epileptic specimens,precipitating an increased neuronal discharge and induction of seizures.This review aims to provide an overview of experimental findings that implicated astrocytic modulation of extracellular K^+ in the mechanism of epileptogenesis.展开更多
This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride cotransporters.These carriers contribute to the path...This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride cotransporters.These carriers contribute to the pathogenesis of hypertension via regulation of intracellular chloride concentration in vascular smooth muscle and neuronal cells and via sensing chloride concentration in the renal tubular fluid,respectively.Both NKCC1 and NKCC2 are inhibited by furosemide and other high-ceiling diuretics widely used for attenuation of extracellular fluid volume.However,the chronic usage of these compounds for the treatment of hypertension and other volume-expanded disorders may have diverse side-effects due to suppression of myogenic response in microcirculatory beds.展开更多
基金supported partially by Helen Vosburg Mc Crillus PlummerRobert Edward Lee Plummer,Jr.Chair in Neurosurgery(to JHH)NIH-R01-NS-067435(to JHH)
文摘The contribution of an impaired astrocytic K^+ regulation system to epileptic neuronal hyperexcitability has been increasingly recognized in the last decade.A defective K^+ regulation leads to an elevated extracellular K^+ concentration([K^+]o).When[K^+]o reaches peaks of 10-12 mM,it is strongly associated with seizure initiation during hypersynchronous neuronal activities.On the other hand,reactive astrocytes during a seizure attack restrict influx of K^+ across the membrane both passively and actively.In addition to decreased K^+ buffering,aberrant Ca^2+ signaling and declined glutamate transport have also been observed in astrogliosis in epileptic specimens,precipitating an increased neuronal discharge and induction of seizures.This review aims to provide an overview of experimental findings that implicated astrocytic modulation of extracellular K^+ in the mechanism of epileptogenesis.
基金This work was supported by grants from the Canadian Institutes for Health Research(MOP-81392)(S.N.O.)Russian Foundation for Fundamental Research##14-04-31705(S.V.K.),15-04-00101(S.N.O.)+1 种基金the Russian Scientific Foundation#14-15-00006(S.N.O.)the USA National Institutes of Health Award R01-GM85058(N.O.D.).
文摘This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride cotransporters.These carriers contribute to the pathogenesis of hypertension via regulation of intracellular chloride concentration in vascular smooth muscle and neuronal cells and via sensing chloride concentration in the renal tubular fluid,respectively.Both NKCC1 and NKCC2 are inhibited by furosemide and other high-ceiling diuretics widely used for attenuation of extracellular fluid volume.However,the chronic usage of these compounds for the treatment of hypertension and other volume-expanded disorders may have diverse side-effects due to suppression of myogenic response in microcirculatory beds.
