Sarcoplasmic Reticulum Function in Smooth Muscle - Physiological ...

114 SUSAN WRAY AND THEODOR BURDYGA
F. Summary 148
IX. Elemental Calcium Signals From Smooth Muscle Sarcoplasmic Reticulum 148
A. Ca sparks 148
B. Ca puffs 152
X. Sarcoplasmic Reticulum and Plasmalemmal Ion Channels 153
A. Overview of Ca-activated ion channels 153
B. BK channels 153
C. SK and IK channels 154
D. Ca-activated Cl channels 155
XI. Sarcoplasmic Reticulum and Development and Aging 156
XII. Gender 156
XIII. pH, Metabolism, and Sarcoplasmic Reticulum Function 157
A. Introduction 157
B. pH 157
C. Metabolism 158
XIV. Mathematical Modeling 158
XV. Conclusions and Future Directions 158
Wray S, Burdyga T. Sarcoplasmic Reticulum Function in Smooth Muscle. Physiol Rev 90: 113–178, 2010;
doi:10.1152/physrev.00018.2008.—The sarcoplasmic reticulum (SR) of smooth muscles presents many intriguing
facets and questions concerning its roles, especially as these change with development, disease, and modulation of
physiological activity. The SR’s function was originally perceived to be synthetic and then that of a Ca store for the
contractile proteins, acting as a Ca amplification mechanism as it does in striated muscles. Gradually, as investigators
have struggled to find a convincing role for Ca-induced Ca release in many smooth muscles, a role in controlling
excitability has emerged. This is the Ca spark/spontaneous transient outward current coupling mechanism which
reduces excitability and limits contraction. Release of SR Ca occurs in response to inositol 1,4,5-trisphosphate, Ca,
and nicotinic acid adenine dinucleotide phosphate, and depletion of SR Ca can initiate Ca entry, the mechanism of
which is being investigated but seems to involve Stim and Orai as found in nonexcitable cells. The contribution of
the elemental Ca signals from the SR, sparks and puffs, to global Ca signals, i.e., Ca waves and oscillations, is
becoming clearer but is far from established. The dynamics of SR Ca release and uptake mechanisms are reviewed
along with the control of luminal Ca. We review the growing list of the SR’s functions that still includes Ca storage,
contraction, and relaxation but has been expanded to encompass Ca homeostasis, generating local and global Ca
signals, and contributing to cellular microdomains and signaling in other organelles, including mitochondria,
lysosomes, and the nucleus. For an integrated approach, a review of aspects of the SR in health and disease and
during development and aging are also included. While the sheer versatility of smooth muscle makes it foolish to
have a “one model fits all” approach to this subject, we have tried to synthesize conclusions wherever possible.
I. INTRODUCTION AND BRIEF
HISTORICAL OVERVIEW
For an excellent general historical overview of the
sarcoplasmic reticulum (SR) and endoplasmic reticulum
(ER), the recent review by Verkhratsky (728) can be
consulted. For other general references to the SR (or ER),
Ca homeostasis and SR/ER Ca-ATPase (SERCA), the following
reviews are recommended: Laporte et al. (384),
Pozzan et al. (573), Karaki et al. (336), Strehler and
Treiman (665), Floyd and Wray (184), Rossi and Dirksen
(597), Carafoli and Brini (106), Carafoli (105), and Endo
(167).
An internal store of Ca in smooth muscle cells was
postulated following demonstrations of Ca remaining in
the cells after immersion in Ca-free solutions. This followed
older observations that contractile responses,
which were known to be Ca dependent, could continue
for varying periods in Ca-free solutions, and that if external
[Ca] had been elevated before the switch to Ca-free
Physiol Rev VOL 90 JANUARY 2010 www.prv.org
solution, this period was extended (278). Although we
now have a more sophisticated view of Ca handling and
Ca sensitivity (e.g., Refs. 13, 201, 271, 612, 769), which
could also account for contraction in Ca-free solutions,
the conclusion reached, i.e., there must be an internal Ca
store, was correct. Electron microscopy (EM) of smooth
muscle revealed a membranous system of tubules and
sacs, the SR, that was both close to the periphery and
caveolae as well as deep within the cell. Close apposition
of the SR to mitochondria and the nucleus was also noted.
This membrane system excluded extracellular markers
such as ferritin and horseradish peroxidase, but was contiguous
with the lumen of the nuclear envelope. Although
originally described as sparse, following improvements in
fixation and microscopy, these earliest accounts were
replaced with terms such as “well developed” and “rich
reticulum.” It is now appreciated that the SR’s distribution,
amount, and shape is not only smooth muscle specific,
but also changes with physiological stimuli and developmental
stage and in disease.