Lecture 21 Flashcards

1
Q

What does cardiac muscle look like histologically?

A

cylindric, branched cells that have 1-2 nuclei centrally located

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2
Q

What makes up the transverse and lateral components of the intercalated disks?

A

transverse = fascia adherens and desmosomes

lateral = gap junctions (do not allow spatial summation
all cells are interconnected)

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3
Q

Duration of the AP in cardiac muscle?

A

much longer compared to those found in skeletal muscle and neurons

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4
Q

contraction in cardiac muscle?

A
  1. During an AP, the DHP channels (within the T-tubule) open and allows for extracellular calcium to enter the cell.
  2. The extracellular Ca then activates the RyR-2 which releases Ca from the SR
  3. calcium then binds to troponin C
  4. tropomyosin moves away from myosin binding site on actin
  5. Contraction
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5
Q

Relaxation in cardiac muscle?

A
  1. Ca will unbind from troponin due to decreased levels of Ca
  2. tropomyosin again blocks the binding site
  3. Ca is pumped back into the SR (80%) and some is moved to the ECM (20%) by Ca/Na channel
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6
Q

differences between skeletal and cardiac tissue?

A

skeletal cells are multinucleated and the nuclei are peripheral, while cardiac muscle has 1-2 centrally located nuclei

skeletal cells are non-branched while cardiac cells are branched

skeletal = short AP, while cardiac = long AP

Ca just comes from the SR in SM, while Ca comes from the SR and EC in cardiac cells

skeletal cells are isolated, while cardiac cells are all interconnected by gap junctions

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7
Q

Inotropism?

A

the ability of myocardial cells to change force/strength of contraction at cellular level

how?

  1. Increasing Ca influx from DHP channels
  2. increasing release of Ca from RYR-2
  3. sensitizing troponin C to Ca
  4. anrep effect - increase in afterload
  5. bowditch effect - increase heart rate
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8
Q

Gs, Gi, Gq protein receptors on cardiac cells

A

Gs = beta-1 receptor = stimulate muscle contractibility

Gi = M2 receptors = decrease HR and conduction velocity

Gq = increase contraction

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9
Q

Digoxin

A

Beta agonist: Gs protien linked

cardiac glycoside

directly inhibits the Na/K ATPase, which also inhibits the Na/Ca exchanger due to low Na

used for systolic heart failure (increased contraction)

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10
Q

Striated vs smooth muscle regarding muscle contraction

A

striated muscle has Troponin C, while smooth muscle does not.

striated muscle has a sarcomere, while smooth muscle does not.

smooth muscle has caldesmon and calponin as thin filaments

striated muscle = bipolar arrangement and a higher amount of myosin II
smooth muscle = side-polar arrangement and a lower amount of myosin II

Striated= 1:2 thick to thin filament ratio 
smooth = 1:15 thick to thin filament ratio
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11
Q

Multi-unit and single-unit smooth muscle

A

Multi:
each fiber is innervated by a single nerve ending
each fiber can contract independently

single-unit:
electrically coupled (syncytium)
fibers contract together by gap junctions

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12
Q

Smooth muscle contraction and relaxation

A
  1. increased calcium intracellularly
  2. formation of the Ca/calmodulin complex
  3. activation of myosin light chain kinase
  4. phosphorylate myosin light chain
  5. contraction
  6. myosin light chain phosphatase can un-phosphorylate the myosin light chain, thus leading to relaxation

actomyosin ATPase activity is much slower in smooth muscle compared to skeletal muscle

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13
Q

Calcium entry into smooth muscle cells?

A
  1. voltage-gated calcium channels (electromechanical coupling)
  2. ligand-gated calcium channels (pharmacomechanical coupling: contraction with AP)
  3. stretch activated calcium channels
  4. leak calcium channels (unregulated)
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14
Q

Calcium channel blockers

A

inhibit voltage-dependent L-type calcium channels

thus decreased muscle contractibility

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15
Q

Calcium entry using secondary messengers regarding smooth muscle

A
  1. IP3 pathway- increase of calcium
  2. cAMP pathway - either the inhibition of adenylyl cyclase or the activation
    decreased cAMP = muscle relaxation
  3. NO-cGMP pathway- muscle relaxation
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16
Q

Milrinone

A

selective PDE-3 inhibitor

in cardiomyocytes = more cAMP = more Ca = more inotropy and chronotropy

In vascular smooth muscle = more cAMP = inhibition of MLCK = general vasodilation

use:
short-term use for acute decompensated heart failure

17
Q

Release of calcium from the SR in smooth muscle

A
  1. calcium binding to RyR and thus releases Ca from SR
  2. phosphokinase C pathway
    IP3 binds to IP3R and thus releases Ca from SR
18
Q

smooth muscle relaxation

A
  1. decrease Ca concentration in the cell by cell repolarization
  2. reuptake of Ca into the SR by the SERCA pump
  3. Ca efflux by Ca ATPase pump
  4. Na/Ca exchange
19
Q

Latch state?

A

muscle maintains its full force of contraction despite reduced amount of continuing excitation and lesser energy required for comparable sustained skeletal
muscle contraction

Low ATP usage
lower Ca usage requirements

importance: it can maintain prolonged tonic contraction in smooth muscle for hours with little use of energy
cause: myosin dephosphorylation while still attached to actin during the crossbridge cycle

20
Q

calcium sensitization and desensitization

A

Decreased MLCP activity = increase MLC phosphorylation = Ca sensitization

increased MLCP activity = decreased MLC phosphorylation = Ca desensitization