Sarcoplasmic Reticulum Function in Smooth Muscle - Physiological ...
Sarcoplasmic Reticulum Function in Smooth Muscle - Physiological ...
Sarcoplasmic Reticulum Function in Smooth Muscle - Physiological ...
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118 SUSAN WRAY AND THEODOR BURDYGA<br />
FIG. 2. Morphological and functional demonstration of the SR <strong>in</strong> smooth muscle. A and B: <strong>in</strong> freshly isolated smooth muscle cells from gu<strong>in</strong>ea<br />
pig ureter, 3-dimensional live sta<strong>in</strong><strong>in</strong>g of the SR with BODIPY FL-X ryanod<strong>in</strong>e (A) and 2-dimensional pseudo-color image of the SR loaded with<br />
Mag-fluo 4 <strong>in</strong> a -esc<strong>in</strong> chemically sk<strong>in</strong>ned myocyte (B). C and D: pseudo-color images of fluo 4-loaded myocyte show<strong>in</strong>g a spontaneous Ca spark<br />
(C) and a Ca wave (D) <strong>in</strong>duced by 10 mM caffe<strong>in</strong>e. Images were obta<strong>in</strong>ed on Ultraview confocal system with Hamamatsu CCD camera. (From T.<br />
Burdyga, L. Borisova, and S. Wray, unpublished work.)<br />
(635). With the use of three-dimensional image reconstruction<br />
techniques, a network of <strong>in</strong>terconnect<strong>in</strong>g, spirally<br />
shaped tubules, ma<strong>in</strong>ly runn<strong>in</strong>g along the longitud<strong>in</strong>al<br />
axis of the cell, can be seen. This is rem<strong>in</strong>iscent of<br />
earlier descriptions <strong>in</strong> fixed tissue with EM. It is notable<br />
that when uter<strong>in</strong>e cells <strong>in</strong> culture were studied with<br />
antibodies to IP 3Rs and RyRs, a different distribution<br />
was found; they had an homogeneous (diffuse) distribution<br />
and hot spots detected by fluo 3FF, were scattered<br />
throughout the cytoplasm (792). In stomach myocytes<br />
from Bufo mar<strong>in</strong>us, Steenbergen and Fay (661)<br />
used mag-fura 2 and found the SR to be distributed <strong>in</strong> a<br />
punctate manner, but aga<strong>in</strong> with a concentration peripherally<br />
and around the nucleus. Other studies describ<strong>in</strong>g<br />
more or less similar structures, i.e., <strong>in</strong>terlac<strong>in</strong>g<br />
tubules, sacs, and cisternae, and location of the SR,<br />
<strong>in</strong>clude cultured A7r5 (706), mesenteric artery (214),<br />
and portal ve<strong>in</strong> (221). It appears that when different<br />
fluorescent <strong>in</strong>dicators are used, the same pattern of SR<br />
distribution <strong>in</strong> smooth muscle myocytes is observed.<br />
As found with EM studies, these images of the SR<br />
show it to be abundant around mitochondria and cont<strong>in</strong>uous<br />
with the nucleus (221, 635). There may be more<br />
SR <strong>in</strong> a peripheral location <strong>in</strong> phasic muscles (portal<br />
ve<strong>in</strong> and uterus), compared with mesenteric artery and<br />
A7r5 cells, aga<strong>in</strong> consistent with suggestions from EM<br />
studies. Immunosta<strong>in</strong>s and immuno-EM of RyRs <strong>in</strong> vas<br />
deferens and ur<strong>in</strong>ary bladder myocytes also revealed a<br />
Physiol Rev VOL 90 JANUARY 2010 www.prv.org<br />
largely discrete, peripheral distribution for the SR, assum<strong>in</strong>g<br />
that the RyRs represent the entire SR (394, 525).<br />
Ohi et al. (525) also noted colocalization with largeconductance,<br />
Ca-activated K (BK) channels, discussed<br />
further <strong>in</strong> section XB. In a study of aortic SR, Lesh et al.<br />
(394) found a patchy distribution of RyR throughout the<br />
cell but absent from the nuclear region. The occurrence<br />
of frequent discharge sites or hot spots on the SR and<br />
their relation to Ca release events are discussed <strong>in</strong><br />
section IX.<br />
In summary, recent data obta<strong>in</strong>ed by live sta<strong>in</strong><strong>in</strong>g of<br />
native smooth muscle cells have added confidence to<br />
earlier data on SR structure and distribution obta<strong>in</strong>ed<br />
with EM. There is no certa<strong>in</strong>ty about what the dist<strong>in</strong>ction<br />
between peripheral and central SR means <strong>in</strong> terms of SR<br />
components or functional consequences for any particular<br />
smooth muscle. Perhaps because of the considerable<br />
<strong>in</strong>terest <strong>in</strong> local Ca signals from the SR and their relation<br />
to plasma membrane ion channels, the literature<br />
tends to emphasize the peripheral SR, and few studies<br />
have addressed the role of central SR. All phasic<br />
smooth muscles exam<strong>in</strong>ed with confocal techniques<br />
appear to have predom<strong>in</strong>antly peripheral SR. As well as<br />
the <strong>in</strong>teractions between the SR and plasma membrane<br />
and caveolae, there is also <strong>in</strong>terest <strong>in</strong> elucidat<strong>in</strong>g the<br />
functional importance for smooth muscles of hav<strong>in</strong>g<br />
their SR envelop<strong>in</strong>g mitochondria and appear<strong>in</strong>g con-