A voltage operable current is involved in activation-induced ca2+
entry in human lymphocytes while icrac has no apparent role.
Densmore, J. J., D. M. Haverstick, G. Szabo, and L. S. Gray.
Departments of Pathology and Molecular Physiology and Biological
Physics, University of Virginia, Health Sciences Center,
Charlottesville, Virginia 22908
APStracts 3:0189C, 1996.
Presently it is thought that a non-voltage gated current is
responsible for activation-induced Ca2+ entry in non-electrically
excitable cells such as lymphocytes. However, it has also been
proposed that the pathway instead involves a second messenger
regulated Ca2+ channel which is voltage operable where "voltage
operable" is defined as an intrinsic property of the channel
protein(s) rather than a requirement of normal gating. To evaluate
the contribution of these currents to activation-induced Ca2+ influx,
each was examined with respect to its ability to account for Ca2+
influx as reported by Ca2+-sensitive dyes. We identified a set of
reagents, nordihydroguaiaretic acid and various calmodulin
inhibitors, that inhibits Ca2+ entry, blocks the voltage operable
current but leaves the non-voltage gated current unaltered.
Furthermore, nordihydroguaiaretic acid inhibited Ca2+-dependent
proliferation of mitogen activated human peripheral blood mononuclear
cells or Jurkat T cells and specifically blocked Ca2+-dependent
interleukin-2 production by Jurkat T cells to a degree similar to the
immunosuppressant drug cyclosporin A. We also identified compounds,
amiloride and Mn2+, that block the non-voltage gated current but have
no effect on either the voltage operable current or Ca2+ entry.
Correspondingly, amiloride had no effect on Ca2+-dependent
proliferation of Jurkat cells. These observations imply that blockade
of the non-voltage gated current does not block either Ca2+ entry or
Ca2+-dependent lymphocyte proliferation while blockade of the voltage
operable current does. The data suggest that the voltage operable
current may be a mediator of activation-induced Ca2+ entry in
lymphocytes.
Received 1 November 1995; accepted in final form 30 May 1996.
APS Manuscript Number C660-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96