Cardiac Muscle Mechanics Flashcards
Draw, describe, or be able to identify the cardiomyocyte structure including sarcomeres, gap junctions, and the intercalated disc.
See pg. 24
The cardiac muscle is striated skeletal muscle and shows A and I bands. A major difference from skeletal muscle is the large intercalated discs that separate adjacent myocytes. At an intercalated disc, the cell membranes of two adjacent cardiac muscle cells are closely apposed and bound together by gap junctions and desmosomes. These connections structurally stabilize adjacent cells and allow a direct electrical connection between the two muscle cells. Action potentials can travel across an intercalated disc, moving quickly from one cardiac muscle cell to another. T-tubules do exist in cardiac muscle and occur only at the Z-line.
Cardiac muscle cells are uninucleate or binucleate cells (less than skeletal muscle) but because the cardiac muscle cells are mechanically and electrically connected to one another, the entire tissue resembles a single, giant muscle cell. For this reason, cardiac muscle has been called a functional syncytium. In fact it is two syncytia, the atrial syncytium and ventricular syncytium.
Describe the metabolism of cardiac muscle
Cardiac muscle cells are dependent on aerobic metabolism to obtain the energy needed to continue contracting.
The sarcoplasm of a cardiac muscle cell thus contains large numbers of mitochondria and abundant reserves of myoglobin (to store oxygen).
Energy reserves are maintained in the form of glycogen and lipid inclusions.
Describe the differences & underlying mechanisms between sensitivity and contractility
Effectively, this means that the force of contraction will increase as the heart is filled with more blood and is a direct consequence of the effect of an increasing load on a single muscle fiber.
Increased load stretches the myocardium and increases the affinity of troponin C for calcium, leading to an increase in contractile force for a given level of sarcoplasmic calcium. This is called an increase in SENSITIVITY, where tension generation & length are proportional, independent of calcium levels & tension can increase more even when already @ maximum overlap between thick & think filaments.
The force that any single muscle fiber generates is proportional to the initial sarcomere length (known as preload) or equivalently, the end-diastolic volume of the ventricle. In the human heart, maximal force is generated with an initial sarcomere length of 2.2 micrometers, a length which is rarely exceeded in the normal heart.
Describe the calcium entry mechanisms of the cardiomyocyte
Instead of a physical attachment (triad junction) between the L-type calcium channel and the Ryanodine receptor (the endfeet) as is found in skeletal muscle, cardiac muscle uses calcium induced calcium release (CICR) to open the Ryanodine receptor. So no triad junction in cardiomyocte, but they are close together.
During a cardiomyocyte action potential, a small amount of calcium influx through the L-type calcium channels in the T-tubules binds to the Ryanodine receptors in the sarcoplasmic reticulum (SR) and causes the Ryanodine receptor to open. The open Ryanodine receptor allows large amounts of calcium to flow out of the SR lumen into the sarcoplasm, leading to muscle contraction. This process is called calcium induced calcium release small amounts of external calcium can trigger massive calcium release from the SR because of the sensitivity of the ryanodine receptors to calcium. Calcium induced calcium release contributes ~80% of the sarcoplasmic (cytoplasmic) calcium elevation.
Basically a small amount of calcium influx through the sarcolemma is amplified into a large amount of calcium release from the SR and triggers muscle contraction. Thus external calcium contributes ~20% to the cardiomyocyte calcium elevation and twitch.
NOTE: Because of the trans-sarcolemmal influx of Ca++, cardiac muscle is much more sensitive to extracellular [Ca++] than is skeletal muscle, therefore cardiac muscle is also more sensitive to L- type calcium channel blockers.
Describe the calcium clearance mechanisms of the cardiomyocyte
As L-type calcium channels inactivate and the cell begins to repolarize, several calcium clearance systems begin to remove calcium from the sarcoplasm.
First, the sarcoplasmic and endoplasmic reticulum ATPase (SERCA) uses the energy of ATP hydrolysis to pump calcium ions back into the sarcoplasmic reticulum from the sarcoplasm. About 80% of the sarcoplasmic calcium is removed by SERCA.
As the cell repolarizes, the sodium calcium exchanger (NCX) in the sarcolemma resumes “normal operation” and expels 1 calcium ion for every three sodium ions let in. About 15% of the sarcoplasmic calcium is removed by NCX. Secondary active transport.
A small amount of sarcoplasmic calcium ~5% is removed by a second pump, the plasma membrane calcium ATPase (PMCA) pumps calcium out of the cell.
In addition, the mitochondrial calcium uniporter removes a small amount of sarcoplasmic calcium.
Thus the major***calcium clearance mechanism that terminate contraction are SERCA and NCX.
T tubule is
An invagination of the sarcolemma (plasma membrane) into the interior of the cell that conducts the AP
Cardiac AP’s are ____ duration & ____ ion dependent
long duration: the length of the cardiac AP and its refractory period prevent summation, therefore the heart contracts only by Twitch (strong twitches). Recruitment does not occur in the heart either.
Ca2+ dependent, while skeletal is sodium dependent
Cardiac AP’s move via _____ between cells
Gap junctions. See pg. 27 figure.
Cardiac action potentials propagate through gap junctions between cells. Depolarization in one cell increases positive charge within that cell and that causes displacement of positive charges through gap junction and depolarization of the next cell. Action potentials thereby move between adjacent cells by means of charge displacement through gap junctions.
Describe the crossbridge cycle in cardiac muscle
Same as skeletal muscle, calcium binds Troponin C & moves the tropomyosin off the thin filaments so that the myosin head can bind.
1) ATP binds to myosin, causing the myosin head to detach from actin.
2) Myosin ATPase cleaves ATP. Hydrolysis of ATP causes cross bridge, still separated from actin, to change conformation to a “cocked” orientation.
3) A “cross-bridge” forms as the myosin head binds to actin.
4) The myosin head then releases the inorganic phosphate (P), which causes a conformational change in crossbridge to tilted position, constituting the power stroke that drags the actin filament towards the M-line.
5) ADP is then released in the final step of the cycle.
State Starling’s law of the heart
The Frank-Starling law of the heart states that the more the ventricle is filled with blood during diastole, the greater the volume of ejected blood will be during the resulting systolic contraction (directly related to sensitivity principle).
In other words, the ventricle will pump whatever amount of blood you put into it (so the ventricle will develop greater tension to pump a greater amount of blood).
Discuss heart rate & tension changes in the heart
See pg. 31
Tension can be affected if either the sarcoplasmic [Ca++] is altered (e.g. by an inotropic agent) or if the calcium sensitivity of the myofilaments is altered (e.g., by changing initial length).
Cardiac Muscle SA node is spontaneously active and triggers an endogenous heart rate of about 100 beats per minute.
This is normally reduced under the influence of the parasympathetic vagal nerve (ACh release) to about 60 bpm.
Heart rate is increased by sympathetic activation and norepinephrine release. These effects are realized primarily by changing K+ conductances at the SA (sino atrial) node.
List the effects of greater initial length of the cardiomyocyte with respect to maximal tension (Po), velocity of shortening, extent of shortening, work output, and power output of cardiac muscle.
tension (Po) increases
the velocity of shortening increases
the amount of shortening increases
the work of the heart increases
the power delivered by the heart increases
Describe the inotropic agents & effects on the heart
Norepi (sympathetic) is a positive inotropic agent that increases the force of contraction of the heart on B1 adrenergic receptors. Inotropy, unlike sensitivity, is calcium dependent. Positive inotropy allows more Ca2+ into the cell, & the contraction time decreases since calcium clearance uptake is increased w/ adrenergic innervation = heartbeat increases (positive chronotropy).
NOTE: Norepi increases AP amplitude & duration several heartbeats before an increase in tension is detected.
Norepi + B1 adrenergic receptor = increased cAMP, increased PKA, increased Ca2+, increased tension
Describe the difference between sensitivity & contractility & what happens on a calcium vs tension curve
Sensitivity shifts the curve up since it is calcium independent
Contractility shifts the curve to the right since it is calcium dependent
See pg. 38 figure
Describe the change in contractility (inotropy) that occur with Norepi on a Length vs Tension curve
@ a given length, norepi increases the tension produced due to increased entry of Ca++ & shifts the Length vs Tension curve up. This means that more tension can be produced @ the same length.
See pg. 39-41 figure
