TY - JOUR
T1 - Calcium-dependent subthreshold oscillations determine bursting activity induced by N-methyl-D-aspartate in rat subthalamic neurons in vitro
AU - Zhu, Zi Tao
AU - Munhall, Adam
AU - Shen, Ke Zhong
AU - Johnson, Steven W.
PY - 2004/3
Y1 - 2004/3
N2 - We used whole-cell patch recordings in current clamp to investigate the ionic dependence of burst firing induced by N-methyl-D-aspartate (NMDA) in neurons of the subthalamic nucleus (STN) in slices of rat brain. NMDA (20 μM) converted single-spike firing to burst firing in 87% of STN neurons tested. NMDA-induced bursting was blocked by AP5 (50 μM), and was not mimicked by the non-NMDA receptor agonist AMPA (0.6 μM). Tetrodotoxin (1 μM) converted bursts to oscillations of membrane potential, which were most robust when oscillations ranged between -50 and -70 mV. The NMDA bursts were blocked by an elevated extracellular concentration of Mg2+, but superfusate containing no added Mg2+ either reduced or increased burst firing, depending upon the amount of intracellular current injection. Block of K + conductances by apamin and tetraethylammonium prolonged burst duration, but iberiotoxin had no effect. NMDA-induced burst firing and membrane oscillations were completely blocked by superfusate containing no added Ca 2+, and they were significantly reduced when patch pipettes contained BAPTA. Selective antagonists for T-type (mibefradil, 10 μM), L-type (nifedipine, 3 μM), and N-type (ω-conotoxin GVIA, 1 μM) Ca2+ channels had no effect on NMDA burst firing. Superfusate containing a low concentration of Na+ (20 mM) completely abolished NMDA-induced burst firing. Flufenamic acid (10 μM), which blocks current mediated by Ca2+-activated nonselective cation channels (I CAN), reversibly abolished NMDA-depended bursting. These results are consistent with the hypothesis that NMDA-induced burst firing in STN neurons requires activation of either an ICAN or a Na+-Ca 2+ exchanger.
AB - We used whole-cell patch recordings in current clamp to investigate the ionic dependence of burst firing induced by N-methyl-D-aspartate (NMDA) in neurons of the subthalamic nucleus (STN) in slices of rat brain. NMDA (20 μM) converted single-spike firing to burst firing in 87% of STN neurons tested. NMDA-induced bursting was blocked by AP5 (50 μM), and was not mimicked by the non-NMDA receptor agonist AMPA (0.6 μM). Tetrodotoxin (1 μM) converted bursts to oscillations of membrane potential, which were most robust when oscillations ranged between -50 and -70 mV. The NMDA bursts were blocked by an elevated extracellular concentration of Mg2+, but superfusate containing no added Mg2+ either reduced or increased burst firing, depending upon the amount of intracellular current injection. Block of K + conductances by apamin and tetraethylammonium prolonged burst duration, but iberiotoxin had no effect. NMDA-induced burst firing and membrane oscillations were completely blocked by superfusate containing no added Ca 2+, and they were significantly reduced when patch pipettes contained BAPTA. Selective antagonists for T-type (mibefradil, 10 μM), L-type (nifedipine, 3 μM), and N-type (ω-conotoxin GVIA, 1 μM) Ca2+ channels had no effect on NMDA burst firing. Superfusate containing a low concentration of Na+ (20 mM) completely abolished NMDA-induced burst firing. Flufenamic acid (10 μM), which blocks current mediated by Ca2+-activated nonselective cation channels (I CAN), reversibly abolished NMDA-depended bursting. These results are consistent with the hypothesis that NMDA-induced burst firing in STN neurons requires activation of either an ICAN or a Na+-Ca 2+ exchanger.
KW - Brain slice
KW - Burst firing
KW - Firing pattern
KW - Subthalamic nucleus
KW - Whole-cell recording
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U2 - 10.1111/j.1460-9568.2004.03240.x
DO - 10.1111/j.1460-9568.2004.03240.x
M3 - Article
C2 - 15016087
AN - SCOPUS:1642332207
SN - 0953-816X
VL - 19
SP - 1296
EP - 1304
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 5
ER -