-Hsing Kuo

Ultrastructure of airway smooth muscle.

There is an abundance of ultrastructural data in the literature on vascular, visceral, and other smooth muscles; such data on airway smooth muscle, however, are conspicuously missing. Here we present a series of electron micrographs depicting contractile and cytoskeletal elements as well as organelles in porcine trachealis. Myosin thick filaments are present in the relaxed muscle; thick filament density increases substantially when the muscle is activated. Actin thin filaments are present in large excess over the thick filaments; the thin/thick filament ratio is about 31/1 in the relaxed state; this ratio is reduced to about 22/1 when the muscle is activated. The sarcoplasmic reticulum is often found associated with caveolae and mitochondria. Cells within a bundle are well connected by intermediate and gap junctions. The results demonstrate that quantitative morphological analysis of ultrastructure of airway smooth muscle fixed under different functional states is possible and will be essential in elucidating the structural basis of adaptation and contraction of the muscle.

Contractile filament architecture and force transmission in swine airway smooth muscle

It is well known that the cyclic interaction of myosin cross bridges with actin filaments is responsible for force and shortening generation in smooth muscle. The intracellular organization of contractile filaments, however, is still poorly understood. Here, we show electron microscopic and functional evidence that contractile filaments in airway smooth muscle lie parallel to the longitudinal axis of the cell bundle, in contrast to the obliquely arranged filaments depicted in conventional models. The parallel arrangement of contractile filaments is maintained despite the fact that individual cells are spindle-shaped. This is accomplished through filament attachment to membrane-associated dense plaques that are in turn connected to similar structures on neighboring cells. Intracellularly, the parallel arrangement is maintained despite the centrally located nucleus. This is accomplished by attachment of actin filaments to the nuclear envelope and making the nucleus a force transmitting structure. The results suggest that smooth muscle cells in tissue form a mechanical syncytium and are able to function properly only as a group.

Ca2+ signaling in smooth muscle: TRPC6, NCX, and LNats in nanodomains

Following the recent observation of localized cytosolic subplasmalemmal [Na+] elevations (LNats) in rat aortic smooth muscle cells, we discuss here the current evidence for the structural and molecular roles of cytosolic nanodomains at close junctions of the plasma membrane (PM) and sarcoplasmic reticulum (SR) in the generation of LNats. These junctions, the loss of which might contribute to vascular aging and disease, provide a platform for ion metabolism signalplexes and the interaction of localized Na+ and Ca2+ gradients. We moreover suggest the existence in the junctions of a Na+ diffusional barrier as a necessary condition for the generation of LNats. LNats are likely a fundamental feature of near membrane ion signaling in many cell types, and their discovery offers new possibilities for elucidating the mechanism, function and pathogenesis of Na+ and Ca2+ signaling nanodomains.