Interaction of Opioids and Membrane Potential To Modulate Ca 2+ Channels
in Rat Dorsal Root Ganglion Neurons.
Womack, M., and E.W. McCleskey.
Vollum Institute, Oregon Health Sciences University, Portland, Oregon
97201-3098.
APStracts 2:0041N, 1995.
SUMMARY AND CONCLUSIONS
1) Using patch clamp methods, we show that brief prepulses to very positive
voltages increase (facilitate) the amplitude of current through Ca 2+
channels during a subsequent test pulse in some, but not all, dorsal root
ganglion (DRG) sensory neurons. The amplitude of this facilitated current
generally increases when the Ca 2+ channels are inhibited by activation of
the [mu] opioid receptor. 2) The facilitated current is blocked by _-Conotoxin
GVIA, activates in the range of high-threshold Ca 2+ channels, and
inactivates at relatively negative holding voltages. Thus, facilitated current
passes through N-type Ca 2+ channels, the same channels that are inhibited by
opioids and control neurotransmitter release in sensory neurons. 3) Although
maximal facilitation occurs only at unphysiologically high membrane potentials
(above +100 mV), some facilitation is seen following prepulses to voltages
reached during action potentials. After return to the holding potential,
facilitation persists for hundreds of milliseconds, considerably longer than
in other neurons. Brief trains of pulses designed to mimic action potentials
caused small facilitation (19% of maximal) in a fraction (8 of 24) of opioid-
inhibited neurons. 4) We conclude that: a) prepulses to extremely positive
voltages can cause partial recovery of Ca 2+ channels inhibited by opioids;
b) small, but detectable, facilitation is also seen following physiological
stimulation in some DRG neurons. Facilitation, largely considered a
biophysical epiphenomenon because of the extreme voltages used to induce it,
appears to be physiologically relevant during opioid inhibition of Ca 2+
channels in DRG neurons.
Received 18 April 1994; accepted in final form 3 January 1995.
APS Manuscript Number J192-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 3 April 1995.