TY - JOUR
T1 - A spontaneous tonic chloride conductance in solitary glutamatergic hippocampal neurons
AU - Eisenman, Lawrence N.
AU - Kress, Geraldine
AU - Zorumski, Charles F.
AU - Mennerick, Steven
N1 - Funding Information:
This work was supported a gift from the Bantly Foundation (C.F.Z.), and NIH grants NS44041 (L.N.E), GM 47969 (C.F.Z.), AA12951 (C.F.Z.), NS40488 (S.M.) and AA12952 (S.M.).
PY - 2006/11/6
Y1 - 2006/11/6
N2 - GABA-A receptors mediate both phasic synaptic inhibition and more recently appreciated tonic currents in the vertebrate central nervous system. We addressed discrepancies in the literature regarding the pharmacology of tonic currents by examining tonic currents in a controlled environment of dissociated, solitary glutamatergic neurons. We describe a novel tonically active, bicuculline-sensitive chloride conductance that is insensitive to gabazine and to picrotoxin and thus not mediated by conventional GABA receptors. We exclude a significant contribution from small conductance calcium-gated potassium (SK) channels. We also pharmacologically exclude calcium-gated chloride channels, glycine receptors and the chloride current associated with glutamate transport. Finally, we demonstrate that, although small, this current modulates neuronal excitability. We speculate that this tonic current may provide a complementary mechanism for the regulation of neuronal excitability, particularly in regions with low ambient GABA concentrations. We conclude that this bicuculline-sensitive conductance needs to be accounted for in studies of GABA tonic currents, lest it be confused with currents associated with GABA overflow.
AB - GABA-A receptors mediate both phasic synaptic inhibition and more recently appreciated tonic currents in the vertebrate central nervous system. We addressed discrepancies in the literature regarding the pharmacology of tonic currents by examining tonic currents in a controlled environment of dissociated, solitary glutamatergic neurons. We describe a novel tonically active, bicuculline-sensitive chloride conductance that is insensitive to gabazine and to picrotoxin and thus not mediated by conventional GABA receptors. We exclude a significant contribution from small conductance calcium-gated potassium (SK) channels. We also pharmacologically exclude calcium-gated chloride channels, glycine receptors and the chloride current associated with glutamate transport. Finally, we demonstrate that, although small, this current modulates neuronal excitability. We speculate that this tonic current may provide a complementary mechanism for the regulation of neuronal excitability, particularly in regions with low ambient GABA concentrations. We conclude that this bicuculline-sensitive conductance needs to be accounted for in studies of GABA tonic currents, lest it be confused with currents associated with GABA overflow.
KW - Chloride
KW - GABA
KW - Hippocampus
KW - Inhibition
KW - Tonic current
UR - http://www.scopus.com/inward/record.url?scp=33750345599&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2006.08.033
DO - 10.1016/j.brainres.2006.08.033
M3 - Article
C2 - 16987500
AN - SCOPUS:33750345599
SN - 0006-8993
VL - 1118
SP - 66
EP - 74
JO - Brain Research
JF - Brain Research
IS - 1
ER -