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Voltage Oscillations in Xenopus Spinal Cord Neurons: Developmental Onset and Dependence on Co‐activation of NMDA and 5HT Receptors
Author(s) -
ScrymgeourWedderburn John F.,
Reith Carolyn A.,
Sillar Keith T.
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01501.x
Subject(s) - nmda receptor , 5 ht receptor , depolarization , biophysics , membrane potential , tetrodotoxin , hyperpolarization (physics) , agonist , chemistry , neuroscience , receptor , biology , serotonin , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
The development of intrinsic, N ‐methyl‐D‐aspartate (NMDA) receptor‐mediated voltage oscillations and their dependence on co‐activation of 5‐hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis . Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co‐activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D‐2‐amino‐5‐phosphonovaleric acid (APV) or by excluding Mg 2+ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non‐selective 5HT 1a receptor agonist, 5‐carboxamidotryptamine (5CT) and both 5HT‐ and 5CT‐induced oscillations were abolished by pindobind‐5HT 1 , a selective 5HT 1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage‐dependent block of NMDA channels by Mg 2+ , membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg 2+ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage‐dependent Mg 2+ block. When the membrane potential was depolarized by ∼20 mV via depolarizing current injection (to mimic the NMDA‐induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg 2+ saline. The results suggest that intrinsic, NMDA receptor‐mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co‐activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage‐dependent block of the NMDA ionophore by Mg 2+ through activation of receptors with 5HT 1a ‐like pharmacology.