title: Caveolae in smooth muscles: nanocontacts.
abstract: Smooth muscle cell (SMC) caveolae have been investigated by quantitative and qualitative analysis of transmission electron microscopy (TEM) images of rat stomach, bladder and myometrium, guinea pig taenia coli, human ileum, and rat aortic SMCs. Ultrathin (below 30 nm) serial sections were used for examination of caveolar morphology and their connections with SMC organelles. Average caveolar diameter was smaller in vascular SMCs (70 nm, n=50) than in visceral SMCs (77 nm, n=100), but with the same morphology. Most of the caveolae, featured as flask-shaped plasma membrane (PM) invaginations, opened to the extracellular space through a 20 nm stoma (21 +/- 3 nm) having a 7 nm thick diaphragm. A small percentage of caveolae (3%), gathered as grape-like clusters, did not open directly to the extracellular space, but to irregular PM pockets having a 20-30 nm opening to the extracellular space. In visceral SMCs, caveolae were disposed in 4-6 rows, parallel to myofilaments, whilst aortic SMCs caveolae were arranged as clusters. This caveolar organization in rows or clusters minimizes the occupied volume, providing more space for the contractile compartment. The morphometric analysis of relative volumes (% of cell volume) showed that caveolae were more conspicuous in visceral than in vascular SMCs (myometrium - 2.40%; bladder - 3.66%, stomach - 2.61%, aorta - 1.43%). We also observed a higher number of caveolae per length unit of cellular membrane in most visceral SMCs compared to vascular SMCs (myometrium - 1.06/microm, bladder - 0.74/microm, aorta - 0.57/microm, stomach - 0.48/microm). Caveolae increase the cellular perimeter up to 15% and enlarge the surface area of the plasma membrane about 80% in SMCs. Threedimensional reconstructions (15micro(3)) showed that most caveolae, in both visceral and vascular SMCs, have nanocontacts with SR (87%), other with mitochondria (10%) and 3% apparently have no contact with these organelles. Usually, 15 nm wide junctional spaces exist between caveolae and SR, some of them with nanostructural links between each other or with mitochondria: direct contacts (space <2 nm or none) and molecular links, so called 'feet' (about 12 nm electron dense structures between organellar membranes). Direct contacts possibly allow molecular translocation between the two membranes. Electron-dense 'feet'-like structures suggest a molecular link between these organelles responsible for intracellular Ca(2+) homeostasis (excitation-contraction coupling or pharmaco-mechanical coupling). Close appositions (approximately 15 nm) have also been observed between caveolae and perinuclear SR cisternae, suggesting that caveolae might be directly implicated in excitation-transcription coupling.
authors.affiliation: Department of Cellular and Molecular Medicine, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania. lmp@jcmm.org
authors.forename: L M
authors.initials: LM
authors.lastname: Popescu
authors.forename: M
authors.initials: M
authors.lastname: Gherghiceanu
authors.forename: E
authors.initials: E
authors.lastname: Mandache
authors.forename: D
authors.initials: D
authors.lastname: Cretoiu
mesh_terms: D000818:Animals; D001011:Aorta / Q000648:ultrastructure; D021941:Caveolae / Q000648:ultrastructure*; D002467:Cell Nucleus / Q000648:ultrastructure; D003106:Colon / Q000648:ultrastructure; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000648:ultrastructure; D021621:Imaging, Three-Dimensional; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000648:ultrastructure; D009130:Muscle, Smooth / Q000648:ultrastructure*; D009215:Myometrium / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000648:ultrastructure; D013270:Stomach / Q000648:ultrastructure; D001743:Urinary Bladder / Q000648:ultrastructure