Conversion between permeability states of inositol 1,4, 5
-trisphosphate receptors in cultured smooth muscle cells.
Sugiyama, Takao, and William F. Goldman.
Departments of Physiology and Medicine, University of Maryland
School of Medicine and the Geriatric Research, Education and Clinical
Center, Baltimore Veterans Administration Medical Center, Baltimore,
Maryland 21201
APStracts 2:0244C, 1995.
The kinetics of the effect of inositol 1,4,5-trisphosphate (InsP3) on
Ca2- in the sarcoplasmic reticulum (SR) were studied in saponin
-permeabilized A7r5 cells. At 0.1 (M, InsP3 elicited slow
monoexponential declines in SR free Ca2-, [Ca2-]SR. For [InsP3] =
0.2-100 (M, evoked declines in [Ca2-]SR were biphasic and best fit as
the sum of two first-order processes with rate constants kfast and
kslow. kfast varied as a function of [InsP3] over the range tested,
while kslow was already maximal when [InsP3] = 0.1 (M. To analyze SR
Ca2- release elicited by InsP3, the rate constants for InsP3-induced
changes in the total SR Ca2- content (kR) were calculated. kR was
accurately described only when both [Ca2-]SR and [InsP3] were
considered together. kR was dependent on InsP3 binding to receptors
that existed in either of 2 states, a high affinity-low conductance
state (InsP3RH) and a low affinity-high conductance state (InsP3RL).
The permeability of InsP3RL was 12.28 time larger than that of
InsP3RH, and the conversion between permeability states as well as
changes in both the affinity and cooperativity with which InsP3 was
bound to InsP3RL were mediated by SR Ca2-. This SR Ca2- -dependent
modulation of the characteristics of InsP3 receptors forms the basis
for the biphasic time-course characteristic of InsP3-evoked SR Ca2-
release.
Received 28 February 1995; accepted in final form 31 May 1995.
APS Manuscript Number C112-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.