Smooth muscle cells are adapted for slow, sustained contractions reducing the lumina of the tubular structures in which they occur. These are often paced by networks of interstitial cells of Cajal. The latter are recurrently depolarised by Ano1-Cl- channel opening, triggered by inositol trisphosphate induced store Ca2+ release. This triggers T-type Ca2+ current causing propagating slow waves then transmitted, via gap junctions, to smooth muscle cells. The resulting smooth muscle cell activation by L-type Ca2+ channels elicits Ca2+-induced sarcoplasmic reticular Ca2+ release. Additional autonomic and local transmitter driven pharmacomechanical coupling mechanisms mediated by a range of G-proteins also promote second-messenger-mediated muscle contraction or relaxation. Cross-bridge activity is activated by a combined Ca2+-calmodulin-mediated caldesmon dissociation from thin filament actin and myosin light chain kinase activation. Termination of cross bridge cycling leads to either muscle relaxation or latch-bridge formation, permitting sustained shortening in an absence of ATP-dependent energy expenditure.