Organization of Ca2+ stores in vascular smooth muscle: functional implications.
Much evidence suggests that caffeine/ryanodine (Caf/Ry)-releasable and inositol-1,4,5-trisphosphate (InsP3)-releasable Ca2+ stores in the sarcoplasmic reticulum (SR) of smooth muscles are at least partially distinct. We directly visualized SR stores in primary-cultured rat mesenteric artery myocytes with high-resolution digital imaging and the low-affinity Ca2, indicator, Furaptra (Kd = 75.6 microM). The SR appears to be a continuous tubular network. Nevertheless, SR Ca2+ stores are organized into small, separate, functionally independent compartments. Cyclopiazonic acid (CPA; inhibits SR (Ca2+ pump) and Caf (or Ry) release Ca2+ from different, spatially distinct compartments. Similar heterogeneity is seen with serotonin (acts via InsP3), which unloads only the CPA-sensitive compartments. Some of the SR ('junctional' SR; jSR) lies within 12-15 nm of the plasmalemma (PL). The jSR, the overlying PL microdomains, and the intervening, tiny volume of cytosol form junctional complexes ('PLasmERosomes'). Na+ pumps with high-ouabain-affinity alpha2 or alpha3 subunits, Na+/Ca2+ exchangers, and store-operated channels are confined to these PL microdomains, whereas Na+ pumps with low-ouabain-affinity alpha1 subunits and plasma membrane Ca2+ pumps are uniformly distributed. As a result of this organization, low-dose ouabain can selectively modulate Na+ and Ca2+ concentrations in the PLasmERosomes and jSR Ca2+ stores, and can thereby regulate Ca2+ signalling.
Blaustein
Mordecai P
MP
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
Golovina
Vera A
VA
Song
Hong
H
Choate
Jacqueline
J
Lencesova
Lubomira
L
Robinson
Shawn W
SW
Wier
W Gil
WG
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D027682:Cation Transport Proteins / Q000378:metabolism; D008322:Mammals; D008955:Models, Cardiovascular; D032342:Muscle Cells / Q000502:physiology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D002118:Calcium