AVS 271 Anatomy and Physiology

1. AVS 271 � Anatomy and Physiology Handout 18 October 22, 2008 Muscle Physiology Chapter 7

2. Smooth Muscle Found in the wall of hollow tubular organs of the gastrointestinal and reproductive tracts; blood vessels; urinary bladder; air ways in the lungs, and other locations Does not have the striated banding pattern found in skeletal and cardiac muscle Not under direct voluntary control Contractile activity is primarily regulated by the autonomic nervous system and hormones

3. Smooth Muscle cont. Cells are joined by gap junctions Provide electrical and physical connections between cells Allows a group of muscle cells to contract together as a unit Contraction in smooth muscle cells occurs due to cross � bridge movements between myosin and actin, but their organization and the process of excitation � contraction coupling is quite different than striated muscle

4. Smooth Muscle Cell Structure Single nucleus Can divide throughout life Contain actin and myosin filaments oriented diagonally across the cell NOT organized into myofibrils Contraction does occur due to sliding filament action

5. Smooth Muscle Contraction Regulated by calcium Mechanism is much different than skeletal muscle Thin filaments do not contain troponin or tropomyosin Calcium regulates the enzyme that phosphorylates myosin (�energizing� the myosin cross bridge) Sources of calcium: Sarcoplasmic reticulum Not arranged in any specific pattern in relation to the filaments, but closely associated with the plasma membrane Extracellular fluid

6. Sequence of Smooth Muscle Contraction Increased concentration of calcium in smooth muscle cell Calcium binds to calmodulin Calmodulin is structurally related to troponin Calcium � calmodulin complex allosterically activates the enzyme myosin � kinase Active myosin � kinase then uses ATP (already bound to myosin) to phosphorylate the myosin cross bridge (i.e., covalent modulation) Energizes the cross bridge and enables it to bind to actin

7. Smooth Muscle Contraction cont. The energized (i.e., phosphorylated) myosin cross bridge can then bind to actin and undergo a cross � bridge (contraction) cycle Myosin is then dephosphorylated by myosin � phosphatase, which is continuously active in smooth muscle cells Can occur before or after ATP binds to myosin and causes the cross bridge to detach If myosin is dephosphorylated before ATP attaches, the cross bridge will remain attached to actin maintaining continued muscle tension (without use of energy)

8. Smooth vs. Skeletal Muscle

9. Regulation of Smooth Muscle Contraction Many inputs to a smooth muscle cell can regulate its contractile activity Can be stimulatory or inhibitory May or may not involve a change in membrane potential Neural input from autonomic nervous system Sympathetic and parasympathetic neurons via neurotransmitters Hormones Classical (oxytocin) and local (prostaglandins)

10. Muscle Patho � Physiology

11. Muscle Cramps Spontaneous, involuntary, painful, sudden contractions of skeletal muscles Can occur in any muscle, but calf and foot muscles most common �True� cramps are associated with spontaneous repetitive firing of motor unit action potentials at rates up to 150 / second During the cramp, muscle is visibly and palpably taut and painful, often with abnormal posture of the affected joint

12. Etiology of Muscle Cramps Idiopathic: Nocturnal leg cramps in elderly Exercise � related Metabolic disorders Intense exercise in hot weather, pregnancy, uremia, Acute extracellular volume depletion Hemodialysis Lower motor neuron disorders Medications Hereditary disorders

13. Hyperkalemic Periodic Paralysis (HyPP)in Horses Autosomal dominant genetic disorder Traces back to the QH stallion �Impressive� H / H Severely affected H / N Heterozygous carrier N / N unaffected

14. Hyperkalemic Periodic Paralysis (HyPP) Clinical signs: Brief period of increased muscle tone Sweating and muscle fasciculations +/- muscle cramping Progressive muscle weakness Dog � sitting position Recumbency +/- increased heart and respiratory rates May be fatal

15. Etiology of HyPP Mutation in a key part of the gene for the skeletal muscle sodium channel This voltage � gated channel is responsible for rapid membrane depolarization during an action potential The mutation causes the membrane to be closer to threshold than normal Elevated serum potassium levels can result in the failure of sodium channels to inactivate Results in persistent depolarization of muscle cells

16. Treatment / Management of HyPP Administer diuretics that increase renal elimination of potassium E.g., acetazolamide Decrease intake of potassium Diet should contain no more than 1% potassium on a dry � matter basis for horses that are not working or lactating Alfalfa hay tends to be relatively high in potassium Grass hay and cereal grains (corn, oats and barley) tend to be lower in potassium

17. Bovine Milk Fever (Parturient Paresis) Typically occurs within 72 hours of parturition, primarily in dairy cows Clinical signs: Excitable, but able to stand Unable to stand, but maintain sternal recumbency Continued loss of conciousness (coma) May be fatal if untreated Etiology: Severe hypocalcemia (low blood calcium level) due to rapid onset of milk production Acute depletion of serum calcium

18. Bovine Milk Fever (Parturient Paresis) Pathophysiology: Calcium is required for release of acetylcholine at the neuromuscular junction Inability to release acetylcholine causes muscle paralysis by blocking neural transmission Calcium is required for muscle contraction Causes muscle paralysis Treatment: Intravenous administration of calcium (slowly) Prevention: Provide feeds with low calcium prior to parturition

19. Capture Myopathy of Wild Animals Acute muscle disease associated with capture and restraint of some wild animals Some species are more susceptible than others Bighorn Sheep and Mountain Goats more susceptible? Incidence is influenced by the method of capture Netting vs. chemical immobilization, etc. Associated with hyperthermia

20. Capture Myopathy of Wild Animals �If bighorn sheep are allowed to struggle for more than 10 or 15 minutes, even when the ambient temperature is low, they may become hyperthermic and suffer capture myopathy� Cited in: Zoo and Wild Animal Medicine: Current Therapy 4. Fowler and Miller, 1999