Cardiac muscle

Overview
'Cardiac muscle' is a type of involuntary striated muscle found within the heart. Its function is to "pump" blood through the circulatory system by contracting.

Metabolism
Cardiac muscle is adapted to be highly resistant to fatigue: it has a large number of mitochondria enabling continuous aerobic respiration; numerous myoglobins (oxygen storing pigment); and a good blood supply, which provides metabolic substrate and oxygen. The heart is so tuned to aerobic metabolism that it is unable to pump sufficiently in ischaemic conditions. At basal metabolic rates, about 1% of energy is derived from anaerobic metabolism. This can increase to 10% under moderately hypoxic conditions, but under more severe hypoxic conditions, not enough energy can be liberated by lactate production to sustain ventricular contractions.

Under basal aerobic conditions, 60% of energy comes from fat (free fatty acids and triacylglycerides), 35% from carbohydrates, and 5% from amino acids and ketone bodies. However, these proportions vary widely according to nutritional state. E.g., in starvation, lactate can be recycled by the heart. There is a cost to lactate recycling, since one NAD+ is reduced to get pyruvate from lacate, but the pyruvate can then be burnt aerobically in the TCA cycle, liberating much more energy.

In diabetes, more fat and less carbohydrate is used, due to the reduced induction of GLUT4 glucose transporters to the cell surfaces. However, contraction itself plays a part in bringing GLUT4 transporters to the surface. This is true of skeletal muscle, but relevant in particular to cardiac muscle, since it is always contracting.

Initiation
Unlike skeletal muscle, which contracts in response to nerve stimulation, and like single unit smooth muscle, cardiac muscle is myogenic, meaning that it is self-excitable stimulating contraction without a requisite electrical impulse coming from the central nervous system.

A single cardiac muscle cell, if left without input, will contract rhythmically at a steady rate; if two cardiac muscle cells are in contact, whichever one contracts first will stimulate the other to contract, and so on. This inherent contractile activity is heavily regulated by the autonomic nervous system. If synchronization of cardiac muscle contraction is disrupted for some reason (for example, in a heart attack), uncoordinated contraction known as fibrillation can result.

This transmission of impulses makes cardiac muscle tissue similar to nerve tissue, although cardiac muscle cells are notably connected to each other by intercalated discs. Intercalated discs conduct electrochemical potentials directly between the cytoplasms of adjacent cells via gap junctions. In contrast to the chemical synapses used by neurons, electrical synapses, in the case of cardiac muscle, are created by ions flowing from cell to cell, known as an action potential.

Intercalated disc
An intercalated disc is an undulating double membrane separating adjacent cells in cardiac muscle fibers. Intercalated discs support synchronized contraction of cardiac tissue. They can easily be visualized by a longitudinal section of the tissue.

Three types of membrane junctions exist within an intercalated disc—fascia adherens, macula adherens, and gap junctions.

Fascia adherens are anchoring sites for actin, and connects to the closest sarcomere. Macula adherens stop separation during contraction by binding intermediate filaments joining the cells together, also called a desmosome. Gap junctions allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle. When observing cardiac tissue through a microscope, intercalated discs are an identifying feature of cardiac muscle

Rate
Specialized pacemaker cells in the sinoatrial node normally determine the overall rate of contractions, with an average resting pulse of 72 beats per minute.

The central nervous system does not directly create the impulses to contract the heart, but only sends signals to speed up or slow down the heart rate through the autonomic nervous system using two opposing kinds of modulation:
 * (1) sympathetic nervous system (fight or flight response)
 * (2) parasympathetic nervous system (rest and repose)

Since cardiac muscle is myogenic, the pacemaker serves only to modulate and coordinate contractions. The cardiac muscle cells would still fire in the absence of a functioning SA node pacemaker, albeit in a chaotic and ineffective manner. This condition is known as fibrillation. Note that the heart can still beat properly even if its connections to the central nervous system are completely severed.

Role of calcium
In contrast to skeletal muscle, cardiac muscle cannot contract in the absence of extracellular calcium ions as well as extracellular potassium ions. In this sense, it is intermediate between smooth muscle, which has a poorly developed sarcoplasmic reticulum and derives its calcium across the sarcolemma; and skeletal muscle which is activated by calcium stored in the sarcoplasmic reticulum (SR).

The reason for the calcium dependence is due to the mechanism of calcium-induced calcium release (CICR) from the SR that must occur under normal excitation-contraction (EC) coupling to cause contraction.

Striation
Cardiac muscle exhibits cross striations formed by alternation segments of thick and thin protein filaments which are anchored by segments called Z-lines.

The primary structural proteins of cardiac muscle are actin and myosin. The actin filaments are thin causing the lighter appearance of the I bands in muscle, while myosin is thicker and darker lending a darker appearance to the alternating A bands in cardiac muscle as observed by a light enhanced microscope.

T-Tubules
Another histological difference between cardiac muscle and skeletal muscle is that the T-tubules in cardiac muscle are shorter, broader and run along the Z-Discs. There are fewer T-tubules in comparison with Skeletal muscle. Additionally, cardiac muscle forms dyads instead of the triads formed between the T-tubules and the sarcoplasmic reticulum in skeletal muscle.

Intercalated Discs
Under light microscopy, intercalated discs appear as thin, typically dark-staining lines dividing adjacent cardiac muscle cells. The intercalated discs run perpendicular to the direction of muscle fibers. Under electron microscopy, an intercalated disc's path appears more complex. At low magnification, this may appear as a convoluted electron dense structure overlying the location of the obscured Z-line. At high magnification, the intercalated disc's path appears even more convoluted, with both longitudinal and transverse areas appearing in longitudinal section. Gap junctions (or nexus junctions) fascia adherens (resembling the zonula adherens), and desmosomes are visible. In transverse section, the intercalated disk's appearance is labyrinthine and may include isolated interdigitations.