What type of skeletal muscle fibers are cardiac muscle analagous to and why?
Type I oxidative: rich blood supply, rich in mitochondria, highly oxygen dependent, slow fatigue
What are similarities and differences btwn skeletal and cardiac muscle?
striated, contains same basic contractile proteins forming thick and thin filaments orgainzed into sarcomeres
have same sliding filament mechanism
have myofibrils, T-tubules, SR
cardiac muscle cells contain intercalated discs (desmosomes, fascia adherens, gap junctions). are an effective syncitium due to gap junctions and all cells are recruited at once.
force generation and its control by Ca2+ are also very similar to skeletal muscle, although cardiac muscle is less dependent on the release of Ca2+ from the SR and mechanism of Ca2+ release is different (Ca2+ induced Ca2+ release)
cardiac muscle cells are much shorter and are sometimes branched
cardiac SR is more sparse
T-tubules are near Z-line vs A-I band junction in skeletal muscle
SR terminal cisternae make junctional couplings with T-tubules called dyads (vs triads in skeletal muscle)
T-tubules are larger in cardiac muscle-does not allow for as much accumulation of ions-avoids hyperkalemia
cardiac muscle CANNOT contract in absence of extracellular Ca2+
What is the myoplasmic Ca2+ concentration dependent upon?
- amount of Ca2+ stored in SR
- amount of Ca2+ that enters from extracellular space
Ca2+ enters the cell through DHP receptors [L-type Ca2+ channels (and T-type?)] and exits the SR by calcium-induced calcium release via RyR. How is the Ca2+ concentration decreased to allow for relaxation?
Ca2+ pumps in the SR (SERCA)
Ca2+ pumps in the sarcolemma (similar to SERCA but not identical)
Na+/Ca2+ exchanger in sarcolemma
To increase force of contraction in skeletal muscle, recruitment of fibers and summation is used. Why can't these mechanisms be used in cardiac muscle to increase force production?
Recruitment of fibers cannot be used bc due to gap junctions, all myocytes (with connections) contract at once
Summation cannot be used bc of the prolonged cardiac AP. By the end of the AP, cardiac muscle has mostly relaxed. This is a protective mechanism. The prominent plateau of the AP results in a long refractory period and the mechanical response is almost complete by the end of the refractory period. There is also a slower rise in contractile force due to a slower increase in intracellular Ca2+ (as compared to skeletal muscle) due to cardiac muscle dependence on Ca2+ current
What is the difference btwn the length-tension relationship and generation of force in skeletal vs cardiac muscle?
The basic shape of the length-tension rship is essentially the same btwn the two muscle. The major diffrnce is the nomrla operating range of the two types of muscle. Skeletal muscle normally operates near the peak of its length-tension curve (where optimal overlap btwn thick and thin filaments is achieved for max tension).
Cardiac muscle operates at less than optimal length-its fibers are much stiffer. Additional stretch of cardiac fibers leads to the generation of additional force. If the heart fills with more blood than usual (which stretches the muscle fibers) the force generated by the next heartbeat will automatically be increased resulting in increased ejection of blood. This mechanims of intrinsic regulation is referred to as Frank-Starling's Law of the Heart.
How is passive tension maintained in cardiac myocytes? What is the mechanism behind this?
When cardiac muscle is stretched, passive tension increases substantially which prevents overstretching of the heart. Titin and collagen produce most of the passive force. Titin also maintains the precise structural arrangement of thick and thin filaments. This is a major determinant of diastolic force.
The mechanims underlying such a stretch-induced increase in force of contraction appears to involve an increase in Ca2+ sensitivity of actin-myosin interacions. Also evidence that Ca2+ sensitivity of active force is under the strong influence of the titin-based lattice spacing modulation. Therefore, titin is a self-adjustable and multi-functional spring that is indispensible for proper heart functions.
What factors increase the length of venticular cardiac muscle fibers? What factors decrease their length?
increase length of ventricular fibers
- stronger atrial contractions
- increase in total blood volume
- increase in venous tone
- increased pumping action of skeletal muscle
- increase negative intrathoracic pressure (increases pressure gradient btwn periphery and right atrium which increases venous retunr and leads to a larger preload)
decrease length of ventricular fibers
- standing (decrease in venous return)
- increase in intrapericardial pressure
- decrease in ventricular compliance
What parts of the cardiac cycle to the pictures correlate with? (answer in terms of left ventricle, but could also be right)
A: Muscle is relaxed and bears no weight. For the intact LV, this situation is analgous to the relaxed ventricle after ejection when the aortic valve is closed and the left ventricular pressure has not yet decreased enough for the mitral valve to open-isovolumetric relaxation
B: Resting muscle is stretched by a preload which represents end diastolic volume (EDV)
C: Resting muscle is still stretched by the preload, but the afterload has been added without allowing the muscle to be further stretched. This is analgous to isovolumetric contraction when the ventricle is contracted with the mitral valve closed as well as aortic valve bc left ventricular pressure has not yet exceeded aortic pressure
D: Ventricle has contracted (isotonic contraction) and lifted the afterload. This represents the left ventricular ejection into the aorta. During ejection, afterload is represented by aortic and intra-ventricular pressures which are virtually equal to each other.
What factors can influence preload and afterload?
Preload and afterload depend on certain characteristics of the vascular system and heart. The degree of vascular tone and peripheral resistance influence preload and afterload. A change in HR or SV can also alter preload and afterload.
Contractility, or inotropic state, of cardiac muscle is a measure of the force developed by the muscle fibers when the initial fiber length remains constant (at a given preload). At the cellular level, inotropic state is a function of what?
Inotropic state is a function of the rate of cross-bridge cycling btwn actin and myosin filaments. More cycling=increased contractility=increased force
Increased intracellular Ca2+ concentration leads to increased contractility
How may the inotropic state of cardiac muscle be altered at the level of the cell and the whole heart?
At level of cell
Nervous system and hormonal inputs, many drugs
(catecholamines-NE and E, cardiac glycosides/digitalis, Ca2+ channel blockers) xanthines: caffeine and theophylline-pos inotropic agents bc inhibit break down of cAMP
At level of whole heart: decrease in number of functional myocytes (MI), decreased coronary artery supply
True or false: Increased force due to addtional stretch of cardiac muscle (Frank-Starling's Law) is different from increased force due to increased myoplasmic Ca2+ concentration. In both cases, force devloped increases. However, in the case of Frank-Starling'sLaw this takes place due to decreased initial fiber length (at constant myoplasmic Ca2+). At cellular level, increased contractility is due to increased myoplasmic Ca2+ with muscle fibers at the same intial fiber lenght. These 2 mechanisms can work simultaneously.
Compare a hypodynamic heart (such as in heart failure) with a hyperdynamic heart (such as heart stimulated by NE) as it pertains to end-diastolic pressure, rise of ventricular pressure, and ejection phase.
hypodynamic heart: characterized by an elevated end-diastolic pressure (EDP), slowly rising ventricular pressure, and a somewhat reduced ejection phase
hyperdynamic heart: characterized by a reduced EDP, fast rising ventricular pressure, and brief ejection phase
Note that the slope of the ascending limbs in the graph indicates maximal rate of force development by ventricles (max rate of change in pressure with time). At any given degree of ventricular filling, slope provides and index of the intial contraction velocity and hence of contractility.