MINI 3 Questions

Intercalated disks are the cell junctions between the cardiac muscle fibers. These are unique to cardiac muscle cells. They are interdigiting folds of sarcolemma at the end of adjacent cells, linking them structurally and functionally.

1 or 2 large, oval, centrally located nuclei.

*Some other characteristic features of cardiac muscle cells are lipfuscin granules, cytoplasmic branching, and intercalated disks.

The transverse portion stains like a dark plaque consists of zonula adherens (anchor actin filaments) and desomosomes (bind cells together and prevent separation during contraction).

The longitudinal portion consists of gap junctions (ionic continutiy; ionic coupling, spreading of depolarization).

1) Diad instead of triad: No well-developed terminal cisternae as in skeletal muscle, only small terminal cisterna present beside the T tubule. Together they are called the diad (one terminal cisternae and one T tubule). Diads are located at the level of the Z lines (whereas in skeletal muscle the T tubules and triad are located at the A band/I band junction); T tubules are larger and lined by external lamina.

2) Mitochondria in cardiac muscle cells: more and larger

3) Myofibrils: are not completely separated from each other due to the less developed sarcoplasmic reticulum.

One type of special cardiac muscle cell are modified cardiac muscle cells they function like neurons and neurofibers; they form a conducting system in the heart -- they generate action potential, initiate contraction, transmit action potential to all parts of the heart.

The nodes and fibers are both made up of the modified cardiac muscle cells. The first node is the sino-atral (SA) node which occurs at the junction of the superior vena cava and right atrium. The second node is the atrio-ventricular (AV) node which occurs in the septum between the two atria.

SA node are the pacemaker cells, they spontaneously generate action potentials, and thus the rate of AP's determines the pace of the heart. They send this AP to the other node which is then transmitted to the Bundle of His, and Punkinje Fibers to all the parts of the heart.

Also, sympathetic and parasympathetic fibers that terminate at nodes only modify the rate of intrinsic cardiac muscle contraction.

Cardiac endocrine cells are specialized muscle cells located primarily in the atrial wall and in the interventricular septum.

Produce small peptides hormones (atrial natriuretic polypeptide). ANP decrease the renal tubules to resorb Na+ and H2O (i.e. increase Na+ and H2O loss).

Natriuresis & Diuresis = Down regulate BP

Dark secretory granules in a histology slide are indicative of cardiac endocrine cells.

Cardiac muscle is capable of undergoing hypertrophy (exhibited in many hypertensive patients). Cardiac muscle cells do not have regenerative capacity; dead muscle cells are replaced by connective tissue (scar tissue) (which cannot contract and threfore weakens the heart)

*CMC hypertrophy is a pathological condition

-Skeletal and cardiac muscle are striated, smooth muscle is not
-Skeletal muscle is multinucleated, while cardiac muscle has 1 or 2 large, oval, centrally located nuclei.

Unlike skeletal muscle, there is no NMJ in cardiac muscle cells. Also in CMCs, the ryanodine receptor and dihydropyridine receptor is not physically coupled. The sarcoplasmic reticulum is not as developed in cmc as it is in skeletal muscle. Thus in cmc, the ligand for the ryanodine receptor isn't the DHP receptor, rather it is Ca2+. The calcium will come in through the DHP receptor, bind to the ryanodine receptor --- so a calcium dependent ryanodine receptor is necessary to open to the calcium stores in the sr.

There is spontaneous depolarization and automaticity of the conducting cells of the heart. They will (if left to their own devices), during their rest phase (phase 4), spontaneously depolarize.

Remember because cardiac muscle cells are joined through gap junctions in the intercalated disk, one cell depolarizing and causing an AP will cause the adjacent cells to as well.

Ex: Cells in the SA node, have the fastest rate of spontaneous depolarization, so they during phase 4 trigger an AP and spontaneously depolarize first. The AP will then transmit to the atrial muscle, then to the AV node, down the bundle branches to the Purkinje fibers (located in the inner ventricular walls of the heart, in the sub-endocardium, are larger than cardiac muscle cells, but have fewer myofibrils, and no T-tubules, may contain intercalated disks). onto the ventricular muscle cells. Purkinje cells have been shown to be linked to ordinary cardiac fibers by gap junctions and desmosomes. These gap junctions allow propagation of depolarization from Purkinje fibers to cardiac muscle myofibrils.

It's called the slow response pacemaker AP because of the speed of the depolarization once the membrane potential is brought to threshold.

Rest Phase:
Depolarization Phase
Repolarization Phase

If we start at phase 0, what occurs when we get to threshold is that instead of VGSC, we now have VGCC to open. Slow L-Type Calcium channels if you remember, are the same names we call those DHP receptors, they open in response to a change in voltage. When they open, calcium flows into the cell depolarizes the membrane. When we get to a peak, the calcium channels begin to close, and some potassium channels open. Just like in the neuronal system, the opening of potassium channels, allows for K+ to leave the cell, repolarizing the membrane, bringing it back down to its resting membrane potential. But what happens here is that now we have a specialized channel, the Funny (f) channel, which opens at that very hyperpolarized membrane potential, and what it allows through is typically sodium current. That influx of sodium when that channel opens up at the very hyperpolarized membrane potential slowly allowing sodium to come through will slowly depolarize the membrane. So it spontaneously (the opening of the channel) depolarizes the membrane, that causes another calcium channel to open, the T type calcium channel, which gives it that little burst past that membrane resting membrane potential to bring it up to threshold, and then we have the L-type calcium channels that open.

SLOW RESPONSE DO NOT HAVE VGCCs

The spread of depolarization from neighboring cells will cause these cells to reach threshold, and that's going to cause the opening of voltage gated sodium channels just like in the neuronal system. This causes a very fast depolarization. Then the VGSC's will become inactivated, and VGPCs will open causing an initial repolarization (sometimes this is called the notch phase). Right about when that repolarization starts is when VGCCs are going to open (they are slow to open). When the VGCCs just like when they did in the conducting cells, calcium will come into the cell. That influx of calcium will TRY to cause a depolarization. That depolarization that is being fought with the repolarization from the efflux of potassium ions will produce what looks like a plateau to the membrane potential. This plateau will remain due to the balance between the efflux and influx. Eventually, potassium wins! There are way more potassium channels than there are calcium channels in the heart. Enough potassium channels will take over and repolarization will occur. That repolarization brings us back down to rest, and just like in a neuronal cell, we just leak potassium channels that maintain our membrane resting potential. We then then wait till the next spread of depolarization comes from neighboring cells.

It will be virtually the same as it was in the neuronal system.

AP propagation down T-tubule opening L-type calcium channel, allowing for calcium to enter --- calcium entered binds to RyR, opening it causing an efflux of Ca2+ out of the SR. Ca2+ will bind to troponin, causing a conformation change, moving tropomyosin off of the myosin binding site on actin, allowing for cross bridge cycling to occur, so on so forth.

DIFFERENCES

DHPR + RYR = no longer touching

Na/Ca2+ exchanger powered by the Na/K ATPase

SERCA/PLB, a SR Ca2+-ATPase.

FYI
The rate at which SERCA moves Ca²⁺ across the SR membrane can be controlled by phospholamban (PLB/PLN) under β-adrenergic stimulation. Increased β-adrenergic stimulation reduces association between SERCA and PLB by phosphorylation of PLB. When PLB is associated with SERCA, the rate of Ca²⁺ movement is reduced, upon dissociation of PLB Ca²⁺ movement increases.

There is a lot of mitochondria in the cardiac system. You need every single muscle contraction to occur in order to live. In order to ensure that that occurs, there is tons of need for ATP in the heart system and therefore there is tons of mitochondria, and all of the contraction of the heart depends on aerobic metabolism. There is a lot of oxidative phosphorylation

In the cardiac system, because of the speed of the action potential (due to the plateau phase,) the rise in tension occurs in the middle of that AP. The refractory of that AP doesn't end till the muscle contraction/tension is decreasing. Thus, we cannot have tetani in the cardiac system. This is a good thing, because for every contraction of the muscle cells of the heart, you need a relaxation of the muscle cells of the heart. You need to able to fill the heart with blood, before you pump it out.

For every contraction period (systole), there is a resting period (diastole), during which the heart can fill with blood.