Snapshot A 46-year-old woman with a past medical history of systemic lupus erythematosus comes to the physician’s office for discolored fingers that occur in the winter. She reports that this usually is not very painful and only happens when it is cold outside. Her fingers usually turn white first, then blue, and finally become pink with re-warming. She is prescribed calcium-channel blockers. When asked why this happens, her physician tells her that this is most likely due to an exaggerated vasospasm of the smooth muscles in her blood vessels in response to cold temperatures. (Raynaud phenomenon) Introduction Smooth muscle has bundles of contractile proteins that criss-cross in a lattice across the cell Smooth muscle is able to maintain a high force of contraction for less ATP than skeletal muscles Contraction Rise in intracellular calcium ions (Ca2+) action potential depolarizes plasma membrane L-type voltage-gated Ca2+ channels open, causing intracellular Ca2+ levels to rise Ca2+ are sequestered in sarcoplasmic reticulum inside the cell when excited, Ca2+ channels on sarcoplasmic reticulum membrane open free Ca2+ are released into the cytoplasm Ca2+ bind to calmodulin, which induces conformational change Ca2+-calmodulin (CaM) complex activates the myosin light-chain kinase (MLCK) this phosphorylates myosin light chain (MLC) and triggers actin-myosin binding and smooth muscle contraction Termination of Contraction Nitric oxide nitric oxide is a soluble guanylyl cyclase that produces cyclic guanosine monophosphate (cGMP) cGMP activates protein kinase G, which activates MLCP Myosin light chain phosphatase (MLCP) dephosphorylates and inactivates MLC allowing the myofibrils to relax Sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) pumps Ca2+ from the cytosol back into the sarcoplasmic reticulum