MSK 23 - Muscle Physiology-IV Flashcards
What are the major cardiac muscle specializations that differentiate it from skeletal muscle? What is the importance of these specializations?
- Long absolute refractory periods to prevent tetanic contractions and temporal summation so the heart has time to fill before it contracts
- All cells connected by gap junctions, therefore no spatial summation
- Pacemaker activity, ther is no requirement for outside nerve stimulation for depolarization
- Myofibrils are branched, interlocked with IC discs, and possess stiff collagen fibers for rigidity and increased preload with stretching (starling’s law)
As it applies to excitation contraction coupling, what are six important differences between cardiac and skeletal muscle?
- A nerve doesn’t stimulate the AP across the sarcolemma. That is done by the pacemaker cells in the SA node
- The L-type calcium channel actually functions as a channel and doesn’t contact the RyR receptors in cardiac muscle
- The L-type calcium channel can modified to let more/less Ca++ through (inotropy)
- RyR opening is stimulated by Ca++ that entered from the extracellular environment through the L-type channels.
- During a normal contraction, only about 40% of crosbridges are activated (skeletal is closer to 100%). Important for inotropy
- Myosin ATPase activity is Ca++ sensitive in cardiac muscle
Discuss the relevant steps of excitation contraction coupling in caradiac muscle cells.
What is inotropy and why does it exist?
Inotropy is the phenomenon that an agent (an inotrope) can cause an increase in cardiac muscle contractile force. This is necessary because cardiac muscle cannot use spatial or temporal summation to increase contractile force like skeletal muscle does.
What is lusitropy and why does it exist?
The phenomenon that an agent can cause cardiac muscle contractions to relax more quickly. This is important for increasing heart rate.
What are the two ways to increase the inotropic effect that we need to know?
- An increase in sympathetic activity or a ß1-agonist activates ß1 receptors in cardiac muscle which leads to L-type Ca++ channels being phosphorylated causing them to let more Ca++ into the cell when opened. These leads to more RyR receptor opening and a higher cytosolic [Ca++]. This leads to a more forceful contraction
- The drug digoxin is a cardiac glycoside that inhibits the Na/K ATPase of cardiac muscle cells. This leads to an increase in cytosolic [Na+] which will slow the efflux of Ca++ through the Na/Ca exchanger. This, in turn, increases cytosolic [Ca++] and leads to a more forceful contraction.
What is the way to decrease the inotropic effect that we need to know?
The use of a ß1 blocker will prevent the sympathetic nervous system from increasing the inotropic effect via activation of the ß1 receptor.
What are the ß1 agonists, partial agonists, and antagonists we need to know?
ß1 agonist - dobutamine
ß1 partial agonsits (act as weak antagonists) - pindolol
ß1 antagonist (blocker) - atenolol, metroprolol, propranolol (blocks all ß)
What is the mechanism we need to know that can increase lusitropy?
The activation of the ß1 receptor signaling pathway will lead to SERCA working more efficiently. This will allow muscle to relax more quickly.
Draw the force vs length graphs of active and passive force for skeletal and cardiac muscle. Why are they so different?
Discuss the primary difference in myofilament structure that exists between skeletal and smooth muscle. Why is this important?
This myofilament arrangement (refer to picture) allows smooth muscle to have mysoin crossbridges activated along an entire length of actin. This allows smooth muscle to generate active force over a longer length than skeletal muscle and to generate greater tenstion than smooth muscle.
The attachment of actin filaments to dense bodies instead of Z-lines prevents them from sterically inhibiting each other at shorter lengths. It also allow for generation of greater preload tension.
Draw the force vs length graphs of active, passive, and total force for skeletal and smooth muscle. Why are they so different?
How does myosin cross bridge cycling differ between smooth and skeletal muscle?
In the way the myosin head first binds actin. In skeletal muscle, the myosin head has a high affinity for actin when in its energized state. In smooth muscle, it has a low affinity for actin. In smooth muscle, one of the myosin light chains must become phosphorylated for the already energized myosin head to develop a high affinity for actin and begin the crossbridge cycle.
Discuss how crossbridge cycling initiates in smooth muscle.
How does smooth muscle relaxation occur?
Myosin light chain phosphatases are always active. When cytosolic [Ca++] is high, the phosphatases are outcompeted by the MLCKs. So when cytosolic [Ca++] drops the myosin light chains become unphosphorylated, lose ther affinity for actin, and crossbridge cycling stops.
Draw the velocity vs force graphs for skeletal and smooth muscle. Why is there such a difference?
Facts to know about smooth muscle latch state.
Draw the force vs time graphs for the smooth muscles of sphincters, blood vessels, intestines, esophagus, airways, and urinary bladder.
