Smooth Muscle

List the steps between elevation of cytosolic calcium and increased force

Calcium enters the cytosol via voltage-gated Ca++ channels, other cation channels, voltage-independent Ca++ channels, and from the sarcoplasmic reticulum (triggered by Ca++ or by IP3) Ca binds to calmodulin (CM) to form Ca-CM Ca-CM binds to, and activates, myosin light chain kinase (MLCK) MLCK phosphorylates one of the light chains of myosin, forming myosin- P Myosin-P can interact with actin, forming cross-bridges and cycling to shorten the muscle cell (contraction). If cytosolic calcium levels fall, force can be maintained by dephosphorylating Myosin-P while it is attached to actin. Smooth muscle will always have tone because it will never be fully relaxed due to this cycle of being phosphorylated / dephosphorylated.

Discuss strategies for regulation of vascular tone and relate these strategies to "fight or flight" responses

Innervation: most arteries and arterioles are innervated only by sympathetic nerves, so effects depend on the receptor. NE activates contraction (fight or flight; restrict blood flow to areas that don't need it, like GI tract); ATP opens calcium channels and also causes contraction. NE activates phospholipase C and IP3, which causes the SR to release calcium. Acetylcholine is thought to target the presynaptic nerve and other cells in the vicinity of the smooth muscle, causing them to release factors that influence contractility / relaxation. NO release relaxes the smooth muscle and causes vasodilation. Vascular smooth muscle responds to angiotensin II, and constricts. The endothelium of the vessel is well-coupled to the smooth muscle layer to transmit these signals from the bloodstream. The endothelium produces vasodilators (NO, prostacylin) and vasoconstrictors (endothelin, thromboxane A2) Local signalling also influences smooth muscle tension

Compare and contrast electromechanical and pharmacomechanical coupling mechanisms. Explain why smooth muscle is sensitive to small changes in membrane permeability and why smooth muscle responds to a diverse array of stimuli

Electromechanical coupling mechanisms involve a change in membrane potential that causes a change in the degree of tension in smooth muscle cells. The membrane potential sets the tone of the smooth muscle cell. Cytosolic calcium is controlled through Ca2+ influx via voltage-dependent Ca-channels and subsequent Ca2+-Induced Ca2+-Release (CICR) from internal stores. Pharmacomechanical coupling mechanisms modulate the activity of the cell without altering membrane potential. They bind to receptors and activate signaling cascades, such as the IP3 activation that binds to a receptor on the sarcoplasmic reticulum, causing a release of calcium and contraction of the cell. Both can control Ca2+ release and muscle fiber sensitivity to modulate contraction.

Describe the types of signals that can result in modulated force production by smooth muscles

No unit recruitment due to gap junctions; all cells are recruited at once (unitary smooth muscle) Summation through activation frequency can increase force Length of the muscle affects the force (stretch activates contraction) Signalling cascades can affect calcium levels or sensitivity to calcium and thus the level of tone

Explain why smooth muscle is sensitive to small changes in membrane permeability and why smooth muscle responds to a diverse array of stimuli

Smooth muscle cells are most permeable to potassium, but the permeability is 10 times less than that of skeletal muscle and 100 times less than ventricular muscle. Thus smooth muscle cells have very low permeability; any change in permeability, even a small one, will have large effects on the membrane potential and the degree of contraction of the muscle. - Really important for vasoconstriction and vasodilation. Slow contraction / relaxation; very stable. - Intestinal smooth muscle - regular action potentials / response Smooth muscle has diverse receptor and channel types; thus it can respond to many stimuli in order to change the amount of contractility.

Graph the relationship between tension and length in smooth muscle. Given the absence of sarcomeres in smooth muscle discuss the structural basis of this relationship

The length tension relationship is still based on actin and myosin filaments sliding past each other. However, smooth muscle cells can change the alignment of the thin and thick filaments in order to accommodate stretch (ex: pregnancy - uterus smooth muscle continues to be strong even as it lengthens). Smooth muscle always exists on the ascending part of the graph. The higher the frequency in excitation of the muscle cells, the larger the force.

Draw a picture of a smooth muscle cell highlighting its five major structural features. Distinguish between unitary and multiunit smooth muscle and give examples of each

Unitary smooth muscle contains a large amount of gap junctions, and contains little neural input from the autonomic nervous system. It responds to stretch in the muscle or from neural input to contract, and communicates this with all other cells such that they operate as a unit (unlike skeletal muscle - all interconnected through gap junctions). These cells frequently undergo spontaneous activity (resolve / desolve). Examples include the smooth muscle around blood vessels and of the GI tract. All (unitary) smooth muscle types display tone, a steady level of contractile tension. This means that at any given moment, the muscle can be induced to relax or contract further. Multiunit smooth muscle does not contain gap junctions (more similar to skeletal muscle). Each cell is individually innervated, and coordinated contraction is controlled by the nervous system. Examples of these types of smooth muscle are pilomotor muscles that erect body hair, the vas deferens, the ciliary body and iris of the eye.