Smooth Muscle Flashcards
Describe the structure and organization of smooth muscles
Smooth muscle has thin and thick filaments but lacks organized sarcomeres & T-tubules. The thin filaments are anchored to a cytoskeletal specialization called a dense body. Since there is no regular organization of the the thin and thick filament complexes, smooth muscle lacks A and I bands and is non-striated.
The sarcolemma possess microdomain invaginations called caveolae that are enriched for cell receptors and ion channels (extracellular calcium can enter through the channels).
Describe the role of MLCK and MLCP in the regulation of smoothmuscle contraction and relaxation
Smooth muscle contraction involves Ca2+ binding to calmodulin not Troponin C (like in skeletal or cardiac muscle).
1) Smooth muscle contraction: The key regulatory protein in smooth muscle is myosin light chain kinase (MLCK). Ca++ binds to calmodulin on the myosin light chain kinase (MLCK), resulting in phosphorylation of the regulatory light chain (RLC) of myosin, which turns myosin on. A conformational change in the regulatory light chain (RLC) then permits the myosin to interact with actin.
2) Smooth muscle relaxation: When myosin light chain phosphatase, MLCP, a soluble phosphatase in the sarcoplasm, dephosphorylates the regulatory light chain of myosin, then interaction between actin and myosin is blocked, and the muscle relaxes.
Note that reduction of the concentration of intracellular calcium by calcium ion pumps in the sarcolemma and in the sarcoplasmic reticulum membrane also cause relaxation.
Describe the mechanisms by which smooth muscle develops and maintains tension with a low rate of ATP hydrolysis
The crossbridge cycle in smooth muscle includes an additional step called the “latch- bridge” state. During sustained smooth muscle CONTRACTION it is observed that Ca2+ concentrations in the sarcoplasm fall and myosin light chain becomes dephosphorylated. Despite this, the muscle maintains tension during the sustained contractions. It appears that the latch-bridge state is caused by MLCP dephosphorylation of the myosin light chain while the myosin head IS STILL bound to the actin thin filament. In the latch-bridge state the crossbridge maintains tension and the subsequent dissociation of the myosin head from the actin filament is very slow. Thus in the latch-bridge state, tension is maintained in low sarcoplasmic calcium AND in the absence of phosphorylation of myosin light chain (low ATP). This allows you to maintain tension without burning ATP, thus the low rate of ATP hydrolysis = energetically favorable. Unique to smooth muscle.
However, if MLCP dephosphorylates the myosin light chain while the myosin head is NOT bound to actin, then the myosin is inactive and thus ends the crossbridge cycle.
Describe how adrenaline (epinephrine) cause some smooth muscle to relax and other smooth muscle to contract
During the FIGHT OR FLIGHT response a stimulus (e.g. approaching tiger) causes a massive release of adrenalin (epinephrine) from the adrenal medulla into the blood. The adrenalin circulates in the blood stream and causes vasoconstriction in most arterioles (e.g., skin and gut )* via a1 receptors while causing vasodilation in the arterioles of the skeletal muscle, heart, & bronchiolar smooth muscle in the lung* through b2 receptors. This diverts blood flow and oxygen to the skeletal muscles and heart and opens the airways in preparation for physical exertion.
There are two types of adrenalin receptors found in the smooth muscles in these blood vessels, alpha1 receptors (a1) = vasoconstriction and beta-2 receptors (b-2) = vasodilatation.
b-2 receptors act via G proteins to stimulate adenylate cyclase (AC) which produces cAMP and activates protein kinase A (PKA). PKA then phosphorylates MLCK and inactivates it. This inhibition of MLCK prevents it from being activated by Ca2+ and calmodulin and thus prevents myosin phosphorylation leading to muscle relaxation.
Mnemomic: Vasodialation = Basodialation for B2
Describe charicatristics of a smooth muscle twitch
A smooth muscle twitch is characterized by slow contraction velocity and slow relaxation over longer periods of time, thus resulting in a greater force of smooth muscle contraction with less energy expenditure (ATP hydrolysis).
Unlike the Na + dependent action potential found in skeletal muscle, the smooth muscle action potential is Ca 2+ dependent, meaning that the inward depolarizing current is carried by calcium ions.
Smooth muscle can contract to an extreme to less than 1/3 of initial resting length & it can squeeze lumens (more than skeletal or cardiac).
What are the two sources of calcium for smooth muscle contraction?
extracellular calcium & calcium from the SR
Unitary smooth muscle
Unitary smooth muscle has one axon to many fibers and are electrically coupled to allow AP’s to travel via gap junctions (one to many), and can be spontaneously active (e.g. peristalsis). The term “unitary” refers to smooth muscle in which millions of smooth muscle cells organized in sheets or bundles contract in a coordinated fashion as a single unit.
It responds to stretch, control of contraction by local factors, & has little response to SNS
Multi-unit smooth muscle
Multiunit smooth muscle is composed of discrete smooth muscle fibers, each of which is innervated by its own single nerve ending as in skeletal muscle (one to one). Their contraction is seldom spontaneous. Examples include the smooth muscle fibers of the ciliary muscle and the iris of the eye, and the piloerector muscles that cause erection of the hairs when stimulated by the sympathetic nervous system.
It has little response to stretch, control of contraction by neural factors, & has great response to SNS
Examples of Unitary smooth muscle
Small blood vessels
GI tract
Uterus
Most arteriolar muscle
Note that unitary smooth muscle tends to line the lumens of tubes within the body and contributes to movement of the contents through the tube.
Examples of Multi-unit smooth muscle
Airway smooth muscle
Piloerector muscle
Ciliary muscle of the eye
Some arteriolar muscle
Describe the calcium dependent pathways of smooth muscle contraction & distinguish the electromechanical and pharmacomechanical contraction
1) extracellular calcium enters through the caveoli via L-type Ca2+ channels
2) calcium release through the SR can occur via calcium induced calcium release or via IP3 messenger-IP3 receptor activation of SR calcium channels
3) When SR calcium stores become depleted, the SR signals a plasma membrane calcium channel to open to allow more extracellular calcium into the cell
Electomechanical = AP depolarization or stretch stimulate calcium channel opening
Pharmacomechanical = IP3 ligand binding to cell sufrace receptor made by G-protein coupled receptors which stimulate phospholipase C to make IP3
Describe basal electric rhythym (BER)
rhythmic depolarizations of smooth muscle that are not associated with muscle contraction (subthreshold) during rest. They are different in different organs. When there is sympathetic activation or stretch (or ligand gated process) the subsequent contractions occur on top of the rhythm. So when you stimulate certain smooth muscles you get a particular rhythmic contraction that propagates through the smooth muscle. BER ensures unidirectional contraction so the material is moved one way in the digestive system.
Endothelin
Ligand for smooth muscle contraction with the property of initial relaxation after release (ET-B receptor) & subsequent contraction of smooth muscle (ET-A receptor). Endothelin is released by the endothelium to work on vascular smooth muscle.
ET-B causes relaxation by stimulation of NO release. When ET (endothelin) hits the ET-A receptor (long term), phospholipase C is stimulated & IP3 is released to release Ca2+.
Adenosine binding to the A1 receptor causes vascular smooth muscle relaxation because
A1 receptors (not alpha) are G protein-coupled receptors activate ATP-sensitive potassium channels that causes massive hyperpolarization of the muscle & a decrease in calcium entry.
What type of smooth muscle Ca2+ channels localize to plasma membrane caveolae and are gated primarily by membrane potential change?
L-type Ca2+ channels
L-type Ca2+ channels are voltage gated, opening in response to membrane depolarization. They are found in many cell types, including smooth muscle, where they are concentrated within the plasma membrane pockets called caveolae. Receptor-operated Ca2+ channels open when a ligand binds to the associated receptor, rather than a voltage change. Ca2+ induced Ca2+ release channels and inositol trisphosphate-gated Ca2+ channels are located on the sarcoplasmic reticulum membrane and mediate Ca2+ store release. Store-operated Ca2+ channels are used to top off intracellular Ca2+ stores with extracellular Ca2+ during muscle relaxation. Channel opening is controlled by a store Ca2+ sensor.
