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J Neurophysiol (May 1, 2003). 10.1152/jn.01038.2002
Submitted on Submitted 15 November 2002; accepted in final form 20 January 2003
Department of Physiology, University of Cambridge, Downing Street, CB2 3EG, Cambridge, United Kingdom
Vargas-Caballero, Mariana and
Hugh P. C. Robinson.
A Slow Fraction of Mg2+ Unblock of NMDA Receptors
Limits Their Contribution to Spike Generation in Cortical Pyramidal
Neurons. J. Neurophysiol. 89: 2778-2783, 2003. The timing of voltage-dependent removal of Mg2+
block of N-methyl-D-aspartate receptors
(NMDARs) is potentially critical for determining their nonlinear
contribution to excitability. Here, we measure the kinetics of NMDAR
unblock in nucleated patch and whole cell recordings of rat cortical
pyramidal neurons during depolarizing voltage steps. At room
temperature, the unblock showed a very fast component (
< 1 ms) and a slower component ( = 14-23 ms in nucleated patches).
The slow component accounted for half of the current at +40 mV and its
amplitude and time constant showed some voltage dependence. Blocking
with hyperpolarization was very fast ( < 200 µs).
Voltage-clamp with action potential waveforms, at both room temperature
and at 33°C, showed that the rising phase of single fast action
potentials unblocks far less NMDAR current than expected from the
stationary voltage dependence, while a large amplitude of current is
uncovered during the upstroke of slow calcium action potentials. The
repolarization of fast sodium action potentials uncovers an NMDAR tail
current, much bigger than the stationary level of current.
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