Cardiac & Smooth Muscle

Question 1

What is the cause of hypertrophic cardiomyopathy?

Answer 1

defects in cardiac sarcomeres due to mutations found in 7 genes that contribute to myosin-driven movement

Question 2

What are the differences between skeletal and cardiac muscle E-C coupling?

Answer 2

Cardiac muscle is depolarized via gap junctions

voltage sensors are found close to Ca2+ floodgates (RyR) in cardiac muscle, and directly connected to Ca2+ floodgates in skeletal muscle

Question 3

Why do cardiac muscle cells have different isoforms of RyR that are not directly associated with Cav1.2?

Answer 3

allows for a graded response that is regulated by the ANS, which allows the ANS to adjust strength of contraction

Question 4

What is calcium-induced calcium release (CICR) and which cells use it?

Answer 4

in cardiac muscle cells, external calcium enters through Cav1.2, then binds to RyR to induce their opening and flooding of Ca2+ into the sarcoplasm

Question 5

how is heart rate decreased by the ANS?

Answer 5

PS vagus nerve innervates the SA node and decreases HR by releasing ACh, which binds to mAChRs and stimulates a signaling cascade in SA/AV nodes that hyper polarizes the cells.

Question 6

how is heart rate increased by the ANS?

Answer 6

Sympathetic nerves release norepinephrine at SA and AV nodes, which binds to beta-1 receptors of pacemaker cells - this causes cells to depolarize more quickly via faster K+ channel inactivation and increased opening probability of Na and Ca channels

Question 7

What branch of the ANS controls heart contractility?

Answer 7

sympathetic

Question 8

How does the ANS control contractility of the heart?

Answer 8

Sympathetic postganglionic fibers synapse on cardiac cells and release norepinephrine - binds to B1 receptors - activates Ga(s) cascade, which increases amount of Ca2+ released/heartbeat - increased contractility

Question 9

What is the print phospholamban?

Answer 9

regulates SERCA pumps on the sarcoplasmic reticulum

Question 10

How does phospholamaban regulate HR?

Answer 10

acts as a brake on SERCA pumps - and is turned off by phosphorylation via PKA - which allows for more Ca2+ to be released per beat by increasing available Ca2+ in the SR

Question 11

How do SERCA pumps contribute to contractility?

Answer 11

they pump Ca2+ back into the SR from inside the cell, causing the cardiac cells relax, and maintaining the available Ca2+ in the SR

Question 12

What are the mechanisms for beta-1 stimulation of cardiac contraction?

Answer 12

regulating Cav1.2 channels and SERCA pumps via Ga(s) pathway

Cav1.2 is phosphorylated by PKA and increases their open-probability

SERCA pumps increase their action when PKA phosphorylates their regulatory protein, phospholamban

Question 13

What makes smooth muscle E-C coupling slow?

Answer 13

No T-tubules - action potentials travel only on surface of cells

less SR - fewer Ca2+ stores

Ca2+ sensors not attached to thin filaments

Cross bridges inactive until Ca2+ dependent phosphorylation of myosin

Question 14

Where does smooth muscle obtain Ca2+? why so slow?

Answer 14

via ligand or voltage -gated channels in the plasma membrane - must diffuse across the width of the cell to reach contractile machinery

Question 15

What is the difference between myosin in skeletal versus smooth muscle?

Answer 15

at resting state myosin is phosphorylated (always ready to cycle) in skeletal muscle, but is unphosphorylated/inactive in smooth muscle.

Question 16

How does the use of muscle fibers differ between skeletal and cardiac generation of force?

Answer 16

Skeletal muscle are able to recruit more motor units, but in cardiac muscle, all of the cardiac muscle fibers generate force as a single unit

Question 17

What allows the heart to beat more forcefully when filled?

Answer 17

stretch-activation of muscle fibers (Starling’s Law)

Question 18

Difference between multi-unit and single-unit innervation smooth muscle?

Answer 18

Multiunit - every cell innervated by autonomic post-ganglionic fibers, allows for fine control of force general and allows for sustained contraction.

Single-unit - not all cells are innervated, but action potentials spread via gap junctions - allows for cells to act as a single unit, can be phasic and tonic