MODULATION OF CALCIUM CURRENTS BY ELECTRICAL ACTIVITY.
Li, Minxu, Min Jia, R. Douglas Fields, Phillip G. Nelson.
Laboratory of Developmental Neurobiology, National Institute of Child
Health and Human Development, National Institutes of Health, Bethesda,
APStracts 3:0099N, 1996.
SUMMARY AND CONCLUSIONS
Electrical activation of mouse dorsal root ganglion (DRG) neurons in cultures
for 1-2 days produced a down-regulation of voltage-sensitive calcium currents,
which persisted for 24 hours or more after stimulation was terminated. This
regulation varied with different patterns of activation. Both the magnitude
and time course of regulation of the low threshold voltage activated (LVA) and
high threshold voltage activated (HVA) currents were differentially sensitive
to neural impulse activity. Tonic stimulation at 0.5 Hz did not affect the HVA
currents, but 2.5 Hz did produce a significant decrease. Phasic stimulation
(10 Hz for 0.5 sec every 2 sec) with an average frequency of 2.5 Hz produced
significantly more down regulation of HVA than did the tonic 2.5 Hz
stimulation. The efficacy of phasic stimulation varied inversely with the
interval between bursts. Thus, phasic stimulation of 10 Hz for 0.5 sec but
delivered every 4 sec produced no effects on HVA currents. Stimulation optimal
for down regulation of Ca ++ currents also produced a decreased binding by the
DRG neurons of a L-type Ca ++ channel antagonist. This suggests a down
regulation by electrical activity of the number of Ca ++ channels, rather than
an alteration in a constant number of channels. Depression of LVA currents was
produced by all stimulus patterns tested including 0.5 Hz tonic stimulation.
Chronic stimulation with a stimulation pattern that down regulated Ca ++
currents also produced a slowing of the increase in intracellular Ca ++ (as
measured by Fura-2/AM) which is produced acutely by repetitive stimulation.
This is consonant with earlier studies of [Ca ++ ] i kinetics in growth cones.
Received 11 December 1995; accepted in final form 15 May 1996.
APS Manuscript Number J838-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96