Contraction and Excitation of Smooth Muscles Arsalan Yousuf

1. Contraction and Excitation of Smooth MusclesArsalan Yousuf BS 4th Semester

2. Involuntary non-striated muscles. • Much smaller than skeletal muscles. • Found in blood vessels, in lymphatic vessels, the urinary bladder, uterus, male and female reproductive tracts, gastrointestinal tracts, respiratory tracts, arrectorpili of the skin, ciliary muscle and iris of the eye. • Same principles of contraction and relaxation apply with different physical arrangements

3. Smooth Muscle Types Smooth muscles can be divided into two major types: • Multi unit smooth muscle (operates independantly, innervated by single nerve fiber). • E.g. ciliary and iris muscle of the eye and Arrectorpili muscles of the skin. • Unitary smooth muscle (operates together as a single unit). Also called syncyctial and visceral smooth muscles. • Found in walls of gut, bile ducts, ureters, uterus and blood vessels.

4. Smooth muscle contraction Actin and myosin filaments interact with each other the same way like in skeletal muscles. • Contractile process is activated by Ca2+ • Energy for contraction is yielded from ATP breakdown. • No troponin complex in smooth muscles. • Myosin filaments have what are called “sidepolar” cross-bridges

5. Smooth Muscles

6. Smooth Muscle Contraction as compared to Skeletal Muscle Contraction • Slow cycling of myosin cross bridges along actin filaments. (1/10 to 1/300) • Slow ATPase activity • Cross bridges remain attached for a longer period of time promoting longer time for contraction • Small energy is required for sustained contraction (1/10to1/300 of skeletal muscles) • Slow onset of contraction and relaxation. • Greater force for muscle contraction (4-6 kg/cm2) Skeletal muscles Smooth muscles

7. The Latch Mechanism • Prolonged holding of smooth muscle contractions with little use of energy and little excitatory signal. • Prolonged tonic muscle contractions can remain for hours.

8. Molecular Mechanism of Smooth Muscle Contraction In place of troponin, smooth muscle cells contain a large amount of another regulatory protein called calmodulin. CONTRACTION Action potential causes depolarization of smooth muscle membrane Voltage gated calcium channels open Increased Ca2+ enters the cytoplasm through sarcoplasmic reticulum. Calcium binds with Calmodulin and then forms a complex with enzyme called calmodulin-myosin light chain kinase. The enzyme complex breaks up ATP into ADP and transfers the Pi directly to myosin. This Pi transfer activates myosin. Myosin forms crossbridges with actin (as occurs in skeletal muscle).

9. Figure from Skeletal Muscle contraction lecture RELAXATION Calcium is pumped out of the cell Myosin Light Chain Phosphatase (MLCP) is activated. Mysoin is dephosphorylated and disassociates from actin causing relaxation

10. The Latch Mechanism • Prolonged holding of smooth muscle contractions with little use of energy and little excitatory signal. • Prolonged tonic muscle contractions can remain for hours. Low number of sarcoplasmic reticulum resulting in longer contraction time

11. Calmodulin • Calcium binding messenger protein expressed in all eukaryotic cells. • CaM mediates many crucial processes such as: • inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short term and long term memory and immune response. • CaM can also make use of the calcium stores in the endoplasmic reticulum and the sarcoplasmic reticulum.

12. Neuromuscular Junctions in Smooth Muscles • Nerve fibers form diffuse junctions, that secrete neurotransmitters onto the muscle matrix. • Nerve fibers innervate the outer layer of smooth muscles • Transmitter substances secreted by autonomic nerves in smooth muscles are : • Acetylcholine • Norepinephrine and others.

13. Nervous and Hormonal Control of Smooth Muscle Contraction • Transmitter substances secreted by nerves are : • Acetylcholine • Norepinephrine When acetylcholine excites, norepinephrine inhibits, when NE excites acetylcholine inhibits it

14. Membrane Potentials and Action Potentials in Smooth Muscles • Action potentials in unitary smooth muscles occur in two forms: • Spike potentials • Action potentials with plateaus Spike Potentials: Duration is 10 to 50 mS. They can be generated by electrical stimulation, hormones, neurotransmitters, stretch, spontaneously on its own. Action Potentials with Plateaus: Longer duration, Delayed repolarization, results in prolonged contraction

15. Membrane Potentials and Action Potentials in Smooth Muscles • More voltage gated Ca2+ channels as compared to voltage gated Na+ channels • Flow of Ca2+ ions into the cell is mainly responsible for generation of action potentials. • Ca2+ channels open slowly and remain open for a longer duration resulting in prolonged plateau of action potentials an muscle contractions. SLOW WAVE RYTHM -40 Not an action potential itself Caused mainly due to slow and rapid pumping of positive ions, presumably Na+. Slow waves are also called “pacemaker waves”. 0 -40 -60

16. Smooth Muscle Contraction without Action Potentials • Transmitter substances cause depolarization, this in turn elicits contraction. E.g. iris of the eye. • Smooth muscle fibers are too small to generate an action potential. • When action potentials are elicited in visceral unitary smooth muscle, 30 to 40 smooth muscle fibers must depolarize simultaneously before a self-propagating action potential ensues. • In small smooth muscle cells the local depolarization caused by the nerve transmitter substance itself spreads “electrotonically” over the entire fiber and is all that is needed to cause muscle contraction. • Action potentials can also be generated due to smooth muscle stretch, e.g. contractions in the gut.

17. Effect of local tissue factors and hormones • Effect of O2 and CO2 concentrations on vasodilation. • Hormones like epinephrine, norepinephrine, acetylcholine, angiotensin, endothelin, vasopressin, oxytocin, serotonin and histamine can affect smooth muscle contraction.