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CURE: Digestive Diseases Research Center/Neuroenteric Disease Program, Departments of Medicine and Physiology, University of California at Los Angeles, Los Angeles, California 90024
The mechanisms underlying intracellular
Ca2+ waves induced by either
mechanical or receptor-mediated stimulation of myocytes isolated from
the longitudinal muscle layer of the rabbit distal colon were compared
using fura 2 and fluorescence videomicroscopy. Light focal mechanical
deformation of the plasma membrane or focal application of substance P
resulted in localized intracellular Ca2+ concentration
([Ca2+]i)
transients that propagated throughout the cell. In both cases, the
Ca2+ response consisted of a
transient peak response followed by a delayed-phase response. Substance
P-mediated
[Ca2+]i
responses involved generation of inositol 1,4,5-trisphosphate and
release of Ca2+ from
thapsigargin-sensitive stores, whereas mechanically induced responses
were partially (29%) dependent on
La3+-sensitive influx of
extracellular Ca2+ and partially
on release of intracellular Ca2+
from thapsigargin-insensitive stores gated by ryanodine receptors. The
delayed-phase response in both cases was dependent on extracellular Ca2+. However, although the
response to substance P was sensitive to
La3+, that after mechanical
stimulation was not. In the later case, the underlying mechanism may
involve capacitative Ca2+ entry
channels that are activated after mechanical stimulation but not by
substance P.
smooth muscle; tissue culture; substance P; inositol 1,4,5-trisphosphate; ryanodine receptor; stretch-activated cation channels
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