PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33291778-2 2020 In immature neurons, GABA exerts depolarizing and sometimes functionally excitatory actions, based on active uptake of Cl- by the Na-K-2Cl cotransporter NKCC1. gamma-Aminobutyric Acid 21-25 solute carrier family 12 member 2 Homo sapiens 153-158 32381101-4 2020 Bumetanide, a selective NKCC1 chloride importer antagonist, may attenuate depolarizing GABA action, and in that way reduce disease burden. gamma-Aminobutyric Acid 87-91 solute carrier family 12 member 2 Homo sapiens 24-29 30871970-3 2020 A current view is that the accumulation of intracellular Cl- in neurons as a result of KCC2 down-regulation and/or NKCC1 up-regulation may weaken inhibitory GABA signaling and thereby promote the development of pathological activities. gamma-Aminobutyric Acid 157-161 solute carrier family 12 member 2 Homo sapiens 115-120 33060559-2 2020 Accordingly, developmental disorders such as schizophrenia, Autism Spectrum Disorder, Down syndrome, epilepsy, and tuberous sclerosis complex (TSC) have been associated with alterations in the expression of genes codifying for either of the two cotransporters involved in the excitatory-to-inhibitory GABA switch, KCC2 and NKCC1. gamma-Aminobutyric Acid 301-305 solute carrier family 12 member 2 Homo sapiens 323-328 31930378-1 2020 The GABA response switch from excitatory to inhibitory is a key event in neuronal maturation that depends on the regulated expression of chloride transporters NKCC1 and KCC2. gamma-Aminobutyric Acid 4-8 solute carrier family 12 member 2 Homo sapiens 159-164 31930378-6 2020 Biol.https://doi.org/10.1083/jcb.201903033) describe how degradation of NKCC1 by proteasomes immobilized at the axon initial segment (AIS) by the Ecm29 adaptor contributes to this regulation, driving the GABA switch and the positional maturation of the AIS. gamma-Aminobutyric Acid 204-208 solute carrier family 12 member 2 Homo sapiens 72-77 26441542-3 2015 An accumulation of Cl(-) by the Na(+)-K(+)-2Cl(-) co-transporter (NKCC1) increases the intracellular Cl(-) concentration ([Cl(-)]i) such that GABA depolarizes neuronal precursors and immature neurons. gamma-Aminobutyric Acid 142-146 solute carrier family 12 member 2 Homo sapiens 66-71 30597612-10 2019 Blockade of NKCC1 Cl- cotransporters further controlled interictal discharges in 9 of 12 cases, revealing a Cl- dysregulation affecting actions of GABA. gamma-Aminobutyric Acid 147-151 solute carrier family 12 member 2 Homo sapiens 12-17 26955005-2 2016 NKCC1 (SLC12A2) is a Cl(-)-importing cation-Cl(-) cotransporter that contributes to the maintenance of depolarizing GABA activity in immature neurons, and variation in SLC12A2 has been shown to increase the risk for schizophrenia via alterations of NKCC1 mRNA expression. gamma-Aminobutyric Acid 116-120 solute carrier family 12 member 2 Homo sapiens 0-5 26955005-2 2016 NKCC1 (SLC12A2) is a Cl(-)-importing cation-Cl(-) cotransporter that contributes to the maintenance of depolarizing GABA activity in immature neurons, and variation in SLC12A2 has been shown to increase the risk for schizophrenia via alterations of NKCC1 mRNA expression. gamma-Aminobutyric Acid 116-120 solute carrier family 12 member 2 Homo sapiens 7-14 30977423-5 2019 The primary GABAergic plasticity observed in neuropathic pain includes GABAergic synapse homo- and heterosynaptic plasticity, decreased synthesis of GABA, down-expression of glutamic acid decarboxylase and GABA transporter, abnormal expression of NKCC1 or KCC2, and disturbed function of GABA receptors. gamma-Aminobutyric Acid 12-16 solute carrier family 12 member 2 Homo sapiens 247-252 28057537-3 2017 Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. gamma-Aminobutyric Acid 102-106 solute carrier family 12 member 2 Homo sapiens 0-28 28057537-3 2017 Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. gamma-Aminobutyric Acid 102-106 solute carrier family 12 member 2 Homo sapiens 30-35 27939580-6 2016 Repression of one target, NKCC1, initiates the switch in gamma-aminobutyric acid (GABA) signaling, limits early spontaneous activity, and constrains dendritic growth. gamma-Aminobutyric Acid 57-80 solute carrier family 12 member 2 Homo sapiens 26-31 27939580-6 2016 Repression of one target, NKCC1, initiates the switch in gamma-aminobutyric acid (GABA) signaling, limits early spontaneous activity, and constrains dendritic growth. gamma-Aminobutyric Acid 82-86 solute carrier family 12 member 2 Homo sapiens 26-31 26506510-2 2016 Among them the Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) is responsible for intracellular chloride accumulation in most immature brain structures, whereas the K(+) -Cl(-) co-transporter (KCC2) extrudes chloride from mature neurons, ensuring chloride-mediated inhibitory effects of GABA/glycine. gamma-Aminobutyric Acid 282-286 solute carrier family 12 member 2 Homo sapiens 51-56 25644702-6 2015 This muscimol response switch depends on chloride transporters in the muscles analogous to those that control GABA response in mammalian neurons: the chloride accumulator sodium-potassium-chloride-cotransporter-1 (NKCC-1) is required for the early depolarizing muscimol response, while the two chloride extruders potassium-chloride-cotransporter-2 (KCC-2) and anion-bicarbonate-transporter-1 (ABTS-1) are required for the later hyperpolarizing response. gamma-Aminobutyric Acid 110-114 solute carrier family 12 member 2 Homo sapiens 214-220 24388924-5 2014 Our data identify the 1Na(+):1K(+):2Cl(-) cotransporter 1 (NKCC1) as the major Cl(-)-loader responsible for depolarizing action of GABA/glycine at postnatal days 3-5 (P3-5). gamma-Aminobutyric Acid 131-135 solute carrier family 12 member 2 Homo sapiens 59-64 25495911-3 2015 The Na(+)-K(+)-2Cl(-) (NKCC1) cotransporter blocker bumetanide reduces [Cl(-)]i and causes more negative GABA equilibrium potential in injured neurons. gamma-Aminobutyric Acid 105-109 solute carrier family 12 member 2 Homo sapiens 23-28 25495911-11 2015 CONCLUSIONS: Our data demonstrate a persistent contribution of NKCC1 cotransport in posttraumatic ictal-like activity, presumably as a consequence of chronic alterations in neuronal chloride homeostasis and GABA-mediated inhibition. gamma-Aminobutyric Acid 207-211 solute carrier family 12 member 2 Homo sapiens 63-68 25009229-8 2014 GABA released by interneurons depolarized 65% of pyramidal cells, in which chloride homeostasis was perturbed because of changes in expression of neuronal chloride cotransporters: KCC2 (K-Cl cotransporter 2) was reduced by 42% and expression of NKCC1 (Na-K-2Cl cotransporter 1) increased by 144%. gamma-Aminobutyric Acid 0-4 solute carrier family 12 member 2 Homo sapiens 245-250 25009229-8 2014 GABA released by interneurons depolarized 65% of pyramidal cells, in which chloride homeostasis was perturbed because of changes in expression of neuronal chloride cotransporters: KCC2 (K-Cl cotransporter 2) was reduced by 42% and expression of NKCC1 (Na-K-2Cl cotransporter 1) increased by 144%. gamma-Aminobutyric Acid 0-4 solute carrier family 12 member 2 Homo sapiens 252-276 24695712-2 2014 NKCC1 (SLC12A2) encodes one of two cation chloride cotransporters mediating the conversion of GABA from excitatory to inhibitory. gamma-Aminobutyric Acid 94-98 solute carrier family 12 member 2 Homo sapiens 0-5 24695712-2 2014 NKCC1 (SLC12A2) encodes one of two cation chloride cotransporters mediating the conversion of GABA from excitatory to inhibitory. gamma-Aminobutyric Acid 94-98 solute carrier family 12 member 2 Homo sapiens 7-14 25072038-9 2014 In particular, we will discuss how in some cases, reverting the polarity of GABA responses from the depolarizing to the hyperpolarizing direction with the diuretic bumetanide, a selective blocker of NKCC1, may have beneficial effects on ASDs, thus opening new therapeutic perspectives for the treatment of these devastating disorders. gamma-Aminobutyric Acid 76-80 solute carrier family 12 member 2 Homo sapiens 199-204 24225328-8 2014 Following seizure activity, there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression, resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. gamma-Aminobutyric Acid 192-196 solute carrier family 12 member 2 Homo sapiens 91-96 23964205-1 2013 Early in development, gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mature brain, depolarizes and excites targeted neurons by an outwardly directed flux of chloride, resulting from the peculiar balance between the cation-chloride importer NKCC1 and the extruder KCC2. gamma-Aminobutyric Acid 22-45 solute carrier family 12 member 2 Homo sapiens 272-277 23964205-1 2013 Early in development, gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mature brain, depolarizes and excites targeted neurons by an outwardly directed flux of chloride, resulting from the peculiar balance between the cation-chloride importer NKCC1 and the extruder KCC2. gamma-Aminobutyric Acid 47-51 solute carrier family 12 member 2 Homo sapiens 272-277 22723696-6 2012 Inhibition of NKCC1, but not KCC2, normalizes E(GABA) and restores GABA inhibition of PVN neurons in SHRs. gamma-Aminobutyric Acid 48-52 solute carrier family 12 member 2 Homo sapiens 14-19 23406400-6 2013 A KCC2 expression was downregulated, whereas an NKCC1 expression was upregulated in both the gathering GABA and cortical plate neurons, suggesting these cells had high intracellular Cl(-) concentration rendering GABA action depolarizing. gamma-Aminobutyric Acid 103-107 solute carrier family 12 member 2 Homo sapiens 48-53 23406400-6 2013 A KCC2 expression was downregulated, whereas an NKCC1 expression was upregulated in both the gathering GABA and cortical plate neurons, suggesting these cells had high intracellular Cl(-) concentration rendering GABA action depolarizing. gamma-Aminobutyric Acid 212-216 solute carrier family 12 member 2 Homo sapiens 48-53 23921125-2 2013 We previously reported that SLC12A2-dependent GABA depolarization and DISC1 coregulate hippocampal neuronal development, and 2 SNPs in these genes linked to mRNA expression interactively increase schizophrenia risk. gamma-Aminobutyric Acid 46-50 solute carrier family 12 member 2 Homo sapiens 28-35 23061490-1 2013 Alterations in the balance of K-Na-2Cl cotransporter (NKCC1) and Na-Cl cotransporter (KCC2) activity may cause depolarizing effect of gamma-aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. gamma-Aminobutyric Acid 134-157 solute carrier family 12 member 2 Homo sapiens 54-59 23061490-1 2013 Alterations in the balance of K-Na-2Cl cotransporter (NKCC1) and Na-Cl cotransporter (KCC2) activity may cause depolarizing effect of gamma-aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. gamma-Aminobutyric Acid 159-163 solute carrier family 12 member 2 Homo sapiens 54-59 23061490-2 2013 NKCC1 facilitates accumulation of chloride inside neurons and favors depolarizing responses to GABA. gamma-Aminobutyric Acid 95-99 solute carrier family 12 member 2 Homo sapiens 0-5 22723696-6 2012 Inhibition of NKCC1, but not KCC2, normalizes E(GABA) and restores GABA inhibition of PVN neurons in SHRs. gamma-Aminobutyric Acid 67-71 solute carrier family 12 member 2 Homo sapiens 14-19 22723696-8 2012 Inhibiting NKCC1 N-glycosylation restores E(GABA) and GABAergic inhibition of PVN presympathetic neurons in SHRs. gamma-Aminobutyric Acid 44-48 solute carrier family 12 member 2 Homo sapiens 11-16 22447678-7 2012 Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABA(A)R responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABA(A)R-mediated currents in normal neurons from non-TSC cortical slices. gamma-Aminobutyric Acid 103-107 solute carrier family 12 member 2 Homo sapiens 164-169 21635237-5 2011 Experiments were thus designed to investigate whether, in human epileptic peritumoral cortex, alterations in the balance of NKCC1 and KCC2 activity may decrease the hyperpolarizing effects of GABA, thereby contributing to epileptogenesis in human brain tumors. gamma-Aminobutyric Acid 192-196 solute carrier family 12 member 2 Homo sapiens 124-129 22238092-8 2012 Alternatively, inhibition of the Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1), a Cl(-) importer expressed in most cell types mainly during postnatal development, caused a negative shift in E(GABA) in VP neurons, but had no effect on GABA currents in OT neurons. gamma-Aminobutyric Acid 187-191 solute carrier family 12 member 2 Homo sapiens 33-65 22238092-8 2012 Alternatively, inhibition of the Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1), a Cl(-) importer expressed in most cell types mainly during postnatal development, caused a negative shift in E(GABA) in VP neurons, but had no effect on GABA currents in OT neurons. gamma-Aminobutyric Acid 187-191 solute carrier family 12 member 2 Homo sapiens 67-72 22238092-8 2012 Alternatively, inhibition of the Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1), a Cl(-) importer expressed in most cell types mainly during postnatal development, caused a negative shift in E(GABA) in VP neurons, but had no effect on GABA currents in OT neurons. gamma-Aminobutyric Acid 229-233 solute carrier family 12 member 2 Homo sapiens 67-72 21635237-10 2011 This difference of E(GABA) was abolished by the NKCC1 blocker bumetanide or unblocking of KCC2 with the Zn(2+) chelator TPEN. gamma-Aminobutyric Acid 21-25 solute carrier family 12 member 2 Homo sapiens 48-53 21635237-13 2011 SIGNIFICANCE: We report that the positive shift of E(GABA) in epileptic peritumoral human cortex is due to an altered expression of NKCC1 and KCC2, perturbing Cl(-) homeostasis, which might lead to a consequent reduction in GABAergic inhibition. gamma-Aminobutyric Acid 53-57 solute carrier family 12 member 2 Homo sapiens 132-137 20888891-8 2010 Following a low dose of SP infused into the RVM, intrathecal muscimol (GABA(A) agonist) increased SP-induced thermal hyperalgesia, phosphorylated NKCC1 protein expression, and NMDA NR1 subunit phosphorylation in the spinal cord. gamma-Aminobutyric Acid 71-75 solute carrier family 12 member 2 Homo sapiens 146-151 21733846-1 2011 NKCC1 and KCC2, related cation-chloride cotransporters (CCC), regulate cell volume and gamma-aminobutyric acid (GABA)-ergic neurotranmission by modulating the intracellular concentration of chloride [Cl(-)]. gamma-Aminobutyric Acid 87-110 solute carrier family 12 member 2 Homo sapiens 0-5 21733846-1 2011 NKCC1 and KCC2, related cation-chloride cotransporters (CCC), regulate cell volume and gamma-aminobutyric acid (GABA)-ergic neurotranmission by modulating the intracellular concentration of chloride [Cl(-)]. gamma-Aminobutyric Acid 112-116 solute carrier family 12 member 2 Homo sapiens 0-5 21795557-0 2011 Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. gamma-Aminobutyric Acid 14-18 solute carrier family 12 member 2 Homo sapiens 45-50 21795557-2 2011 We examined the expression of transcripts derived from three genes related to GABA signaling [GAD1 (GAD67 and GAD25), SLC12A2 (NKCC1), and SLC12A5 (KCC2)] in the prefrontal cortex (PFC) and hippocampal formation of a large cohort of nonpsychiatric control human brains (n = 240) across the lifespan (from fetal week 14 to 80 years) and in patients with schizophrenia (n = 30-31), using quantitative RT-PCR. gamma-Aminobutyric Acid 78-82 solute carrier family 12 member 2 Homo sapiens 118-125 20624842-2 2011 During development, gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in adults, typically excites neurons due to high expression of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1). gamma-Aminobutyric Acid 20-43 solute carrier family 12 member 2 Homo sapiens 192-197 20624842-2 2011 During development, gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in adults, typically excites neurons due to high expression of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1). gamma-Aminobutyric Acid 45-49 solute carrier family 12 member 2 Homo sapiens 192-197 20624842-3 2011 NKCC1 facilitates seizures because it renders GABA activity excitatory through intracellular Cl(-) accumulation, while blocking NKCC1 with bumetanide suppresses seizures. gamma-Aminobutyric Acid 46-50 solute carrier family 12 member 2 Homo sapiens 0-5 21042953-1 2011 Early in postnatal life gamma-aminobutyric acid (GABA), the primary inhibitory transmitter in adults, excites targeted neurons by an outwardly directed flux of chloride which results from the unbalance between the cation-chloride cotransporters NKCC1 and KCC2, involved in chloride uptake and extrusion, respectively. gamma-Aminobutyric Acid 24-47 solute carrier family 12 member 2 Homo sapiens 245-250 21042953-1 2011 Early in postnatal life gamma-aminobutyric acid (GABA), the primary inhibitory transmitter in adults, excites targeted neurons by an outwardly directed flux of chloride which results from the unbalance between the cation-chloride cotransporters NKCC1 and KCC2, involved in chloride uptake and extrusion, respectively. gamma-Aminobutyric Acid 49-53 solute carrier family 12 member 2 Homo sapiens 245-250 19004993-7 2009 When the VS-3 neurons were exposed to bumetanide, an antagonist of the Cl(-) transporter NKCC1, the GABA-induced depolarization decreased without any change in firing rate, suggesting that the effects of GABA can be maintained for a long time without additional Cl(-) influx. gamma-Aminobutyric Acid 100-104 solute carrier family 12 member 2 Homo sapiens 89-94 19821838-7 2009 The NKCC1 cotransporter blocker, bumetanide, and L-type calcium channel blocker, nimodipine, attenuated the GABA-induced rise of [Ca(2+)](i). gamma-Aminobutyric Acid 108-112 solute carrier family 12 member 2 Homo sapiens 4-9 19558450-6 2009 The KB-mediated shift in E(GABA) is largely determined by the interaction of the NKCC1 cotransporter and Cl(-)/HCO3 transporter(s). gamma-Aminobutyric Acid 27-31 solute carrier family 12 member 2 Homo sapiens 81-86 19406757-2 2009 In neonates, gamma-aminobutyric acid (GABA) is an excitatory neurotransmitter due to elevated levels of intraneuronal chloride achieved by robust activity of the Na(+)-K(+)-2Cl( -) cotransporter (NKCC1). gamma-Aminobutyric Acid 13-36 solute carrier family 12 member 2 Homo sapiens 196-201 19406757-2 2009 In neonates, gamma-aminobutyric acid (GABA) is an excitatory neurotransmitter due to elevated levels of intraneuronal chloride achieved by robust activity of the Na(+)-K(+)-2Cl( -) cotransporter (NKCC1). gamma-Aminobutyric Acid 38-42 solute carrier family 12 member 2 Homo sapiens 196-201 19277216-8 2009 The shift of E(GABA) from the depolarizing to the hyperpolarizing direction with bumetanide, a blocker of the cation-chloride co-transporter NKCC1, prevented synaptic potentiation and caused synaptic depression, suggesting that the depolarizing action of GABA observed in the presence of CGP55845 is responsible for the potentiating effect. gamma-Aminobutyric Acid 15-19 solute carrier family 12 member 2 Homo sapiens 141-146 19277216-8 2009 The shift of E(GABA) from the depolarizing to the hyperpolarizing direction with bumetanide, a blocker of the cation-chloride co-transporter NKCC1, prevented synaptic potentiation and caused synaptic depression, suggesting that the depolarizing action of GABA observed in the presence of CGP55845 is responsible for the potentiating effect. gamma-Aminobutyric Acid 255-259 solute carrier family 12 member 2 Homo sapiens 141-146 19004993-7 2009 When the VS-3 neurons were exposed to bumetanide, an antagonist of the Cl(-) transporter NKCC1, the GABA-induced depolarization decreased without any change in firing rate, suggesting that the effects of GABA can be maintained for a long time without additional Cl(-) influx. gamma-Aminobutyric Acid 204-208 solute carrier family 12 member 2 Homo sapiens 89-94 17493914-9 2007 If NKCC1 accumulates chloride in ganglion and amacrine cells, deleting or blocking it should abolish the GABA-evoked calcium rise. gamma-Aminobutyric Acid 105-109 solute carrier family 12 member 2 Homo sapiens 3-8 18524541-4 2008 The switch from depolarizing to hyperpolarizing GABA(A)-ergic signaling is triggered through the developmental shift in the balance of chloride cotransporters that either increase (i.e. NKCC1) or decrease (i.e. KCC2) intracellular chloride. gamma-Aminobutyric Acid 48-52 solute carrier family 12 member 2 Homo sapiens 186-191 18497363-6 2008 Bumetanide, a NKCC1 co-transporter antagonist, inhibits generation of IISs and prevents their transformation to ISs, indicating the role excitatory GABA in epilepsies. gamma-Aminobutyric Acid 148-152 solute carrier family 12 member 2 Homo sapiens 14-19 18596173-4 2008 Here, we show in lesioned CA3 hippocampal neurons in vitro and in axotomized corticospinal neurons in vivo that posttraumatic downregulation of the neuron-specific K-Cl cotransporter KCC2 leads to intracellular chloride accumulation by the Na-K-2Cl cotransporter NKCC1, resulting in GABA-induced [Ca2+](i) transients. gamma-Aminobutyric Acid 283-287 solute carrier family 12 member 2 Homo sapiens 263-268 18596173-5 2008 This mechanism is required by a population of neurons to survive in a BDNF-dependent manner after injury, because blocking GABA(A)-depolarization with the NKCC1 inhibitor bumetanide prevents the loss of neurons on BDNF withdrawal. gamma-Aminobutyric Acid 123-127 solute carrier family 12 member 2 Homo sapiens 155-160 18495889-3 2008 During development, GABA, the primary inhibitory neurotransmitter in adults, excites neurons as a result of high expression of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1). gamma-Aminobutyric Acid 20-24 solute carrier family 12 member 2 Homo sapiens 164-169 18495889-4 2008 Using NKCC1 RNA interference knockdown in vivo, we show that GABA-induced depolarization is necessary for proper excitatory synapse formation and dendritic development of newborn cortical neurons. gamma-Aminobutyric Acid 61-65 solute carrier family 12 member 2 Homo sapiens 6-11 17918265-4 2008 Blocking the NKCC1 transporter with bumetanide prevents outward Cl- flux and causes a more negative GABA equilibrium potential (E(GABA)) in immature neurons. gamma-Aminobutyric Acid 100-104 solute carrier family 12 member 2 Homo sapiens 13-18 17918265-4 2008 Blocking the NKCC1 transporter with bumetanide prevents outward Cl- flux and causes a more negative GABA equilibrium potential (E(GABA)) in immature neurons. gamma-Aminobutyric Acid 130-134 solute carrier family 12 member 2 Homo sapiens 13-18 17855601-8 2007 Bumetanide, at doses that selectively block the chloride-importing potassium-sodium-chloride cotransporter NKCC1, produced a hyperpolarizing shift in GABA(A) reversal potentials and suppressed interictal activity. gamma-Aminobutyric Acid 150-154 solute carrier family 12 member 2 Homo sapiens 107-112 18759624-6 2008 Bumetanide, a furosemide-related diuretic already used to treat volume overload in neonates, is a specific inhibitor of NKCC1 at low doses, can switch the GABA equilibrium potential of immature neurons from depolarizing to hyperpolarizing, and has recently been shown to inhibit epileptic activity in vitro and in vivo in animal models of neonatal seizures. gamma-Aminobutyric Acid 155-159 solute carrier family 12 member 2 Homo sapiens 120-125 18497364-9 2008 The NKCC1 co-transporter antagonist bumetanide strongly reduces [Cl(-)]i, GABA-induced depolarization, and network oscillations, confirming the importance of GABA signaling. gamma-Aminobutyric Acid 74-78 solute carrier family 12 member 2 Homo sapiens 4-9 18497364-9 2008 The NKCC1 co-transporter antagonist bumetanide strongly reduces [Cl(-)]i, GABA-induced depolarization, and network oscillations, confirming the importance of GABA signaling. gamma-Aminobutyric Acid 158-162 solute carrier family 12 member 2 Homo sapiens 4-9 18495878-9 2008 Calcium-imaging experiments also indicated that GABA-elicited calcium transients in SCN cells are highly dependent on the NKCC isoform 1 (NKCC1). gamma-Aminobutyric Acid 48-52 solute carrier family 12 member 2 Homo sapiens 122-136 18495878-9 2008 Calcium-imaging experiments also indicated that GABA-elicited calcium transients in SCN cells are highly dependent on the NKCC isoform 1 (NKCC1). gamma-Aminobutyric Acid 48-52 solute carrier family 12 member 2 Homo sapiens 138-143 18495878-11 2008 Together, this work indicates that GABA can play an excitatory role in communication between adult SCN neurons and that this excitation is critically dependent on NKCC1. gamma-Aminobutyric Acid 35-39 solute carrier family 12 member 2 Homo sapiens 163-168 18448640-5 2008 Data from NKCC1(-/-) and bumetanide-exposed neurons indicated that the depolarizing E(GABA) at the AIS is set by chloride uptake mediated by the Na-K-2Cl cotransporter NKCC1. gamma-Aminobutyric Acid 86-90 solute carrier family 12 member 2 Homo sapiens 10-15 18448640-5 2008 Data from NKCC1(-/-) and bumetanide-exposed neurons indicated that the depolarizing E(GABA) at the AIS is set by chloride uptake mediated by the Na-K-2Cl cotransporter NKCC1. gamma-Aminobutyric Acid 86-90 solute carrier family 12 member 2 Homo sapiens 168-173 18256250-0 2008 Thermodynamic regulation of NKCC1-mediated Cl- cotransport underlies plasticity of GABA(A) signaling in neonatal neurons. gamma-Aminobutyric Acid 83-87 solute carrier family 12 member 2 Homo sapiens 28-33 12739168-6 2004 The relative expression level of the neuron-specific SLC12A5 and the Na(+)-K(+)-2Cl(-) cotransporter SLC12A2 appears to determine whether neurons respond to GABA with a depolarizing, excitatory response or with a hyperpolarizing, inhibitory response. gamma-Aminobutyric Acid 157-161 solute carrier family 12 member 2 Homo sapiens 101-108 15845211-9 2005 NKCC1 is important in the maintenance of intracellular Cl(-) in neurons and contributes to GABA-mediated depolarization in immature neurons. gamma-Aminobutyric Acid 91-95 solute carrier family 12 member 2 Homo sapiens 0-5 17319917-3 2007 Alterations in the balance of NKCC1 and KCC2 activity may determine the switch from hyperpolarizing to depolarizing effects of GABA, reported in the subiculum of epileptic patients with hippocampal sclerosis. gamma-Aminobutyric Acid 127-131 solute carrier family 12 member 2 Homo sapiens 30-35 17319917-10 2007 The data suggest that changes in the relative expression of NKCC1 and KCC2 in neurons having aberrant GABA-ergic hyperinnervation may contribute to epileptiform activity in the subicular regions adjacent to sclerotic areas of the hippocampus. gamma-Aminobutyric Acid 102-106 solute carrier family 12 member 2 Homo sapiens 60-65 16709666-5 2006 The NKCC1 blocker bumetanide or a temperature decrease of 10 degrees C shifted the GABA-current E(GABA) more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the E(GABA) of TL neocortex-injected oocytes. gamma-Aminobutyric Acid 83-87 solute carrier family 12 member 2 Homo sapiens 4-9 16709666-5 2006 The NKCC1 blocker bumetanide or a temperature decrease of 10 degrees C shifted the GABA-current E(GABA) more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the E(GABA) of TL neocortex-injected oocytes. gamma-Aminobutyric Acid 98-102 solute carrier family 12 member 2 Homo sapiens 4-9 16709666-5 2006 The NKCC1 blocker bumetanide or a temperature decrease of 10 degrees C shifted the GABA-current E(GABA) more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the E(GABA) of TL neocortex-injected oocytes. gamma-Aminobutyric Acid 98-102 solute carrier family 12 member 2 Homo sapiens 4-9 35524446-4 2022 This would make it impossible even for highly brain-permeant NKCC1 blockers to specifically target depolarizing and excitatory actions of GABA in principal neurons of the brain, which is postulated as the rationale of clinical trials on neonatal seizures. gamma-Aminobutyric Acid 138-142 solute carrier family 12 member 2 Homo sapiens 61-66 14992262-3 2004 In particular, intracellular chloride activity and hence the neuronal response to GABA and glycine appears to be determined by a balance between chloride efflux and influx through KCC2 and the Na+-K+-2Cl- cotransporter NKCC1, respectively. gamma-Aminobutyric Acid 82-86 solute carrier family 12 member 2 Homo sapiens 219-224 12522168-11 2003 Moreover, the GABA-mediated stimulation of NKCC1 activity was not abolished either by removal of extracellular Ca(2+) or BAPTA-AM. gamma-Aminobutyric Acid 14-18 solute carrier family 12 member 2 Homo sapiens 43-48 12522168-13 2003 These results suggest that a GABA-mediated loss of intracellular Cl(-), but not a subsequent rise in [Ca(2+)](i) or shrinkage, leads to stimulation of NKCC1. gamma-Aminobutyric Acid 29-33 solute carrier family 12 member 2 Homo sapiens 151-156 35095429-5 2021 However, in neurons of the immature brain or in neurological disorders such as epilepsy and traumatic brain injury, impaired KCC2 function and/or enhanced NKCC1 expression lead to intracellular Cl- accumulation and GABA-mediated excitation. gamma-Aminobutyric Acid 215-219 solute carrier family 12 member 2 Homo sapiens 155-160 35095429-6 2021 In Huntington"s disease (HD), KCC2- and NKCC1-mediated Cl--regulation are also altered, which leads to GABA-mediated excitation and contributes to the development of cognitive and motor impairments. gamma-Aminobutyric Acid 103-107 solute carrier family 12 member 2 Homo sapiens 40-45 35448033-1 2022 The time-sensitive GABA shift from excitatory to inhibitory is critical in early neural circuits development and depends upon developmentally regulated expression of cation-chloride cotransporters NKCC1 and KCC2. gamma-Aminobutyric Acid 19-23 solute carrier family 12 member 2 Homo sapiens 197-202 35448033-3 2022 The high NKCC1/KCC2 expression ratio decreases in early neural development contributing to GABA shift. gamma-Aminobutyric Acid 91-95 solute carrier family 12 member 2 Homo sapiens 9-14