Sarcoplasmic Reticulum Function in Smooth Muscle - Physiological ...

148 SUSAN WRAY AND THEODOR BURDYGA
nary arterial myocytes (279). In guinea pig colonic myocytes
in the absence of RyR activity, repetitive Ca release
events induced by photolysis of caged IP 3 were not inhibited
by tetracaine or ryanodine (185). This suggests that
IP 3 receptor activity alone accounted for the Ca waves
and loss of the ability of agonists to induce SR Ca release
after caffeine results from Ca depletion in a common
store (185).
F. Summary
From the above we propose that the functional implications
of RyRs in neurotransmitter-induced Ca waves
or oscillations depend on their density relative to IP 3R
and that they share the same store. In smooth muscles
displaying a higher density of IP 3Rs than of RyRs (e.g.,
colonic smooth muscles, Ref. 758), the Ca responses to
neurotransmitters will mainly depend on activation of IP 3
receptors alone (e.g., Ref. 366). In smooth muscles displaying
a higher density of RyRs than IP 3Rs (e.g., rat
portal vein), the Ca waves and oscillations induced by
neurotransmitters will depend on activation of both IP 3Rs
and RyRs. However, comparative functional experiments
correlated with expression and distribution of IP 3R and
RyR channels in other types of smooth muscles are
needed to expand this conclusion to all types of smooth
muscles.
To summarize these data, we can conclude that the
functional studies that employed blockers of SERCAs in
conjunction with activators of IP 3Rs and RyRs shed some
light on the morphological organization of intracellular Ca
stores. In some types of smooth muscles, morphological
studies employing immunofluorescence and molecular biology
techniques provided information that could explain
the functional data. However, to fully understand the
functional role of the SR in smooth muscles, confocal
microscopy and immuno-EM are needed to examine the
relationship between IP 3R and RyR isoforms and SERCA,
to substantiate conclusions drawn from these functional
studies.
IX. ELEMENTAL CALCIUM SIGNALS
FROM SMOOTH MUSCLE
SARCOPLASMIC RETICULUM
A. Ca Sparks
1. Introduction
Calcium sparks were first identified in cardiac (122,
544) and skeletal (354, 708) muscles, where their fundamental
role in the generation of global Ca signals underlying
phasic contractions has been well established. In
smooth muscle cells Ca sparks were first observed in
cerebral artery and showed biophysical and pharmacological
characteristics similar to those of cardiac muscle
cells (507). Since then, similar events have been described
in a wide variety of smooth muscle types including different
types of arteries and arterioles (70, 90, 192, 305, 473,
568, 749, 751), portal vein (219, 221, 474), urinary bladder
(127, 254–256, 288, 312), gastrointestinal tract (34, 35, 220,
223, 351, 808, 809, 811), airways (369, 810), gallbladder
(572), and guinea pig ureter (76, 87). A lack of Ca sparks
has been reported for smooth muscle cells of neonatal
cerebral arteries (213), nonpregnant mouse (476), and
pregnant and nonpregnant rat myometrium (88).
Calcium sparks in smooth muscle can occur spontaneously
(76, 87, 220, 507) or after activation by one of the
following factors: 1) low concentrations (1 mM) of caffeine
(76, 87, 213, 307, 807), 2) elevation of global [Ca]
caused by Ca entering through L-type Ca channels (312,
508), 3) increase in the SR Ca content (87, 811), and
4) stretch (312).
2. Frequent discharge sites
Physiol Rev VOL 90 JANUARY 2010 www.prv.org
Irrespective of the mechanism of activation, Ca
sparks repeatedly arise from a few specialized regions
adjacent to the superficially located SR within the myocytes;
these have been termed FDS (65, 87, 220, 221, 288,
312, 508). These areas are enriched with clusters of RyR2
channels (133, 213, 525). It should, however, also be noted
that frequent discharge events away from the cell membrane
have also been reported in smooth muscle cells
from rat portal vein (18, 65) and gastrointestinal tract
(220, 807). The number of FDS varies not only among
different types of smooth muscle cells (65, 87, 219, 220,
807), but also among different populations of the same
type of smooth muscle (65). The number of FDS is increased
in the presence of low concentrations of caffeine
(76, 307, 807) or after increasing the SR Ca content (87,
811). Such a non-uniform distribution of FDS in smooth
muscle may arise from either the irregular clustering of
RyR Ca release channels, or nonuniform distribution of
the SERCA pump on the SR. Clustering of RyR2 in peripheral
zones of SR was an absolute requirement for the
formation of sites generating spontaneous Ca sparks coupled
to STOCs in arteriolar myocytes (213).
The properties of Ca sparks in isolated cells appear
to be relatively similar in different types of smooth
muscle cells (for details, see reviews in Refs. 536, 750)
and do not differ from those observed in intact preparations
(70, 87, 305, 507, 568). Thus, although variations
in their biophysical parameters have been noted, Ca
sparks appear to be more stereotypic in different types
of smooth muscles than the global Ca signaling controlling
contractility.