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The Journal of Neuroscience, July 1, 2000, 20(13):4855-4863
Excitatory Role of the Hyperpolarization-Activated Inward Current
in Phasic and Tonic Firing of Rat Supraoptic Neurons
Masoud
Ghamari-Langroudi and
Charles
W.
Bourque
Centre for Research in Neuroscience, Montreal General Hospital and
McGill University, Montreal, Quebec H3G 1A4, Canada
The properties and functional roles of the
hyperpolarization-activated inward current
(IH) in magnocellular neurosecretory cells (MNCs) were investigated during sharp microelectrode recordings from supraoptic neurons in superfused explants of rat hypothalamus. Under current clamp, voltage responses to hyperpolarizing current pulses featured depolarizing sags that were abolished by the
IH blocker ZD 7288. Under voltage clamp,
subtraction of current responses to hyperpolarizing steps recorded in
the absence and presence of ZD 7288 was used to investigate the
properties of IH. Current-voltage analysis
revealed that steady-state IH amplitude
increases with hyperpolarization, with half-maximal activation of the
underlying conductance occurring at  78 mV. The time course of
activation of IH during hyperpolarizing
steps was monoexponential with time constants (100-800 msec)
decreasing with hyperpolarization. The effects of ZD 7288 on
IH were slow ( , ~15 min), irreversible, and half-maximal at 1.8 µM. When tested on continuously
active MNCs, application of 30-60 µM ZD 7288 caused a
significant reduction in firing rate. In phasically active MNCs, the
drug decreased burst duration and intraburst firing frequency and
caused an increase in the duration of interburst intervals. These
effects were accompanied with a small hyperpolarization of the membrane
potential. In contrast, ZD 7288 had no effect on spike duration, on the
amplitude of calcium-dependent afterpotentials, or on the frequencies
and amplitudes of spontaneous synaptic potentials. These results
confirm the presence of IH in MNCs of the
rat supraoptic nucleus and suggest that the presence of this
conductance provides an excitatory drive that contributes to phasic and
tonic firing.
Key words:
vasopressin; oxytocin; neurohypophysis; neurosecretory
cell; burst firing; hypothalamus; ZD 7288
Copyright © 2000 Society for Neuroscience 0270-6474/00/20134855-09$05.00/0
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