CVPR 03-24-14 10-11am Cardiac Muscle Structure and Function - Walker Flashcards Preview

â–º Med Misc 16 > CVPR 03-24-14 10-11am Cardiac Muscle Structure and Function - Walker > Flashcards

Flashcards in CVPR 03-24-14 10-11am Cardiac Muscle Structure and Function - Walker Deck (29):
1

Cardiac muscle –what makes it up

Contracilte proteins, myosin & actin (some differences from skeletal muscle forms)

2

Myosin in cardiac muscle

Two heavy chains & four light chains; Developmental & pathophysiological regulation of isoform composition…HC isoform determines ATPase activity (Beta myosin in larger mammals (humans) --> lower ATPase = slower contraction = larger mammals have slower heart beats; alpha myosin is in smaller animals)

3

Actin in cardiac muscle

A contractile protein similar to actin in skeletal muscle; Binds tropomyosin & troponin

4

Types of thin filament regulatory proteins – probably will be question about this!!!

Troponins! Three isoforms: 1. TN-C (Calcium) … 2. TN-I (Inhibitory) …3. TN-T (Tropomyosin)

5

Troponin-C (TN-C)

Binds Calcium; Contains only one Ca2+- binding site (skeletal contains 2)

6

Troponin-I (TN-I)

Iinhibitory; Contains a unique N-terminal extension of 32 amino acids which is highly regulated by phosphorylation (PKA sites); Important for adrenergic responsiveness of the heart; Developmentally regulated (different in fetus & adult)

7

Troponin-T (TN-T)

Bind tropomyosin; Its isoforms are developmentally & pathologically regulated; TM is the only alpha isoform in the heart (unlike skeletal which contains both alpha & beta)

8

Cardiac muscle structure

Composed of interconnected mono-nucleated cells imbedded in a weave of collagen., which contain a large number of myofibrils; Much cell volume is occupied by mitochondria (85% myofibril & mitochondria --> contraction & conduction); Cells are coupled both electrically & mechanically

9

Regulation of Calcium Flow

Depolarization opens L-type calcium channels leading to calcium influx --> Triggers more calcium release from SR through ryanodine receptors (CICR) --> Calcium binding to TN-C triggers contraction --> Calcium is removed by the SR Ca2+-ATPase

10

Cardiac muscle features

Striated (like skeletal muscle); NOT under direct neural control (unlike skeletal) though can be regulated by neural control; Composed of sarcomeres; Cardiac muscle cells are shorter, narrower, and richer in mitochondria than skeletal muscle cells and are usually mononucleated; ATPase activity of myosin is slower in cardiac than skeletal muscle; Ca2+ binding to troponin regulates actomyosin interaction

11

Connections between cardiac muscle cells

Both mechanical & electrical coupling through, allowing synchronized contraction of cells in heart: Intercalated disc (mechanical coupling); Desmosomes; Gap junctions

12

Intercalated discs

Connect cardiac muscle cells w/each other through intercalated discs, which coincide w/ the Z discs of the two adjacent cells, coupling them mechanically

13

Desmosomes

provide adhesion & assure that the force generated in one cell passes to the other

14

Gap junctions

provide low resistance pathways for electrical current

15

Cardiac Sarcomere

Z bands on either end (Z band to Z band = sarcomere) = where actin (thin) filament is tethered; Heavy myosin filaments lie in between actins; M line = no actin, just overlap of myosin

16

Molecular basis of the cross-bridge cycle

Cardiac contraction is a series of interactions between Ca2+, the regulatory proteins and the actomyosin system…In resting muscle, at low intercellular Ca2+, TN-TM complex inhibits actin-myosin combination…. Action potential causes Ca release; Ca iniates contraction; it enter cell and bind Troponin C --> causes conformation change in Troponin I, which is bound to Troponin T, which is bound to Tropomyosin; tropomyosin lies in myosin-binding groove in actin; with Ca, TN-T can pull tropomyosin out of the groove and allow myosin heads to attach (crossbridge), hydrolyze ATP, power stroke, myofilament shortening and muscle contraction

17

Calcium-induced Calcium release

Calcium going into the cells causes more Calcium to be release from the SR; Compared to skeletal muscle, cardiac muscle has less SR, Bigger T Tublues, T tubules in the Z line, and less well-developed T-tubule-SR junctions

18

Removal of Ca from cardiac muscle

Allows cardiac muscle to relax; SERCA (SR Ca2+-ATPase) pump takes up calcium into SR (70% in humans); ~30% removed by SR Na-Ca exchanger and mitochondrial Ca uniporter

19

Regulators of Stroke Volume

PreLoad (directly), Afterload (inversely), Contractiliy (directly)

20

Molecular basis for changes in Preload - Length-tension relationship

When cardiac muscle is stimulated to contract at low resting lengths (low preload), the amount of active tension developed is small…. If you increase muscle length (increased preload), the active tension (and force) developed dramatically increases (up to an optimal length)

21

Molecular mechanisms underlying Length-tension relationship

1. Extent of overlap, 2. Changes in Calcium sensitivity (amt. needed to generate a given force). 3. Increases in Calcium release (stretch-sensitive channels)

22

Afterload – associations/defn.

Most closely associated with aortic (systemic) pressure; Can also be described as the pressure that ventricle has to generate in order to eject blood out of the chamber.

23

Afterload & the Force-velocity relationship

Force-velocity relationship describes the effect of afterload on contractile dynamics….. The greater the afterload, the slower the velocity of shortening (inverse relationship between shortening velocity and afterload)

24

Contractility – defn., regulator

Force with which the heart contracts; Most important physiological regulator is norepinephrine

25

Ionotropes

Substances that change contractility– can be positive or negative

26

Frank-Starling Law of the Heart

STROKE VOLUME of the heart increases in response to an increase in the volume of blood filling the heart (the END DIASTOLIC VOLUME) when all other factors remain constant….Or, AN INCREASE IN PRE-LOAD LEADS TO AN INCREASE IN STROKE VOLUME.

27

Other factors that may contribute to Starlings Law

1. Cardiac titin isoform is very stiff (low compliance)…..2. Ca2+-sensitivity of myofilaments increases as sarcomeres are stretched (same calcium = greater force of contraction)…..3. Closer lattice spacing – stretched sarcomeres have altered spacing between actin & myosin (may result in more force generated per crossbridge).

28

Interrelating cell mechanics with ventricular function

1. increase ventricular volume --> increase in ventricular circumference --> increase in length of individual cardiac muscle cells. 2. At any given volume, increase in tension of individual cells in wall causes increase in intraventricular pressure. 3. As ventricular volume increases, a greater force is required from each individual muscle cell to produce given intraventricular pressure. …….. Law of Laplace: T = P x r/mu

29

Heart disease as a continuum

Although we speak of “hypertrophy, dilation, systolic disease, diastolic disease, etc., heart disease is a continuum of changes and function; (often) not distinct disease

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