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Two distinct oscillatory states determined by the NMDA receptor in rat inferior olive
Author(s) -
Placantonakis Dimitris G.,
Welsh John P.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.t01-1-00123.x
Subject(s) - nmda receptor , cnqx , ampa receptor , dizocilpine , channel blocker , chemistry , phencyclidine , antagonist , biophysics , excitatory postsynaptic potential , calcium , receptor , biology , biochemistry , organic chemistry
1 The effects of N ‐methyl‐ d ‐aspartate (NMDA) receptor activation and blockade on subthreshold membrane potential oscillations of inferior olivary neurones were studied in brainstem slices from 12‐ to 21‐day‐old rats. 2 Dizocilpine (MK‐801), a non‐competitive NMDA antagonist, at 1‐45 μ m abolished spontaneous subthreshold oscillations, without affecting membrane potential, input resistance, or the low‐threshold calcium current, I T . Ketamine (100 μ m ), a non‐competitive NMDA antagonist, and L‐689,560 (20 μ m ), an antagonist at the glycine site of the NMDA receptor, also abolished the oscillations, while the competitive non‐NMDA antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; 20‐50 μ m ) had no effect. 3 NMDA (100 μ m ) induced 4.1 Hz subthreshold oscillations and reversibly depolarized olivary neurones by 13.7 mV. In contrast, 10 μ m α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) and 20 μ m kainic acid depolarized the membrane equivalently but did not induce oscillations. 4 Both NMDA‐induced and spontaneous subthreshold oscillations were unaffected by 1 μ m tetrodotoxin and were prevented by substituting extracellular calcium with cobalt. 5 Removing magnesium from the perfusate did not affect spontaneous subthreshold oscillations but did prevent NMDA‐induced oscillations. 6 NMDA‐induced oscillations were resistant to 50 μ m mibefradil, an I T blocker, in contrast to spontaneous oscillations. Both oscillations were inhibited by 20 μ m nifedipine, an L‐type calcium channel antagonist, and 200 n m ω‐agatoxin IVA, a P‐type calcium channel blocker. Bay K 8644 (10 μ m ), an L‐type Ca 2+ agonist, significantly enhanced the amplitude of both spontaneous and NMDA‐induced oscillations. 7 The data indicate that NMDA receptor activation induces olivary neurones to manifest high amplitude membrane potential oscillations in part mediated by L‐ and P‐ but not T‐type calcium currents. Moreover, the data demonstrate that NMDA receptor currents are necessary for generation of spontaneous subthreshold oscillations in the inferior olive.