Cardiomyocytes are the muscle cells that make up the pumping wall of the heart, and every heartbeat is millions of them squeezing at once. Unlike most muscle you can choose to move, they work on their own, without rest, for a whole lifetime. What makes them remarkable is also their weakness: adults make very few new ones, so the cells you have now are largely the ones you will keep.
What a Heart Muscle Cell Looks Like Inside
Under a microscope, an adult heart muscle cell is a long rod packed end to end with contracting units.1PubMed Central. Biology of the cardiac myocyte in heart disease Its fine dark and light stripes come from neat rows of two proteins, actin and myosin, the same arrangement seen in the muscles of your arms and legs.2Rs. Cardiomyocytes (Cardiac Muscle Cells) – Structure, Function, Cell Biology and Histology That shared pattern is why both are called striated muscle.
Unlike arm and leg muscle, heart cells don’t fuse into long fibers, so most human heart cells have a single nucleus.3Rs. Cardiomyocytes (Cardiac Muscle Cells) – Structure, Function, Cell Biology and Histology Some animals’ heart cells, such as those of rats and mice, usually have two.4PubMed Central. Biology of the cardiac myocyte in heart disease
Each contracting unit holds thin actin filaments and thicker myosin filaments side by side.5PubMed Central. Molecular-scale visualization of sarcomere contraction within native cardiomyocytes Myosin grabs actin and pulls, so the thin filaments slide toward the middle and the unit shortens.6PubMed Central. Molecular-scale visualization of sarcomere contraction within native cardiomyocytes Thousands of units shortening together shorten the whole cell. Single contracting units can flicker and vary from beat to beat even when the whole cell beats steadily.7eLife. Sarcomere dynamic instability and stochastic heterogeneity drive robust cardiomyocyte contraction8eLife. Sarcomere dynamic instability and stochastic heterogeneity drive robust cardiomyocyte contraction The filaments don’t shrink, they overlap more. Relaxing means the filaments slide back apart so the heart can refill with blood.
All this squeezing and relaxing uses constant energy, so a large share of the cell’s volume is taken up by mitochondria sitting between the rows of contracting units. With power stations right next to the filaments, fuel is turned into usable energy close to where myosin does its pulling. Myosin needs energy both to pull and to let go of actin, so a cell short of energy can fail to relax as well as fail to contract.
How Calcium Tells the Cell to Squeeze
Each beat starts as an electrical signal running along the cell’s outer membrane. But the cell is too thick for a surface signal alone to reach its center in time. So the membrane folds inward into tiny tunnels that carry the signal deep into the cell.9PubMed Central. The Physiology and Pathophysiology of T-Tubules in the Heart Where these tunnels meet the cell’s internal calcium store, they form tight contact points that are critical for every beat.10PubMed Central. Cardiac T-Tubule Microanatomy and Function
At those contact points, the signal opens channels that let a small amount of calcium in from outside.11PubMed Central. The Physiology and Pathophysiology of T-Tubules in the Heart That calcium opens release channels on the internal store right next to it, freeing a much larger amount.12PubMed Central. Theory of excitation-contraction coupling in cardiac muscle The more trigger calcium comes in, or the fuller the store, the more calcium is released.13PubMed Central. Modulation of excitation-contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger A dense, orderly network of tunnels lets calcium flood out across the whole cell at the same moment.14PubMed Central. The Physiology and Pathophysiology of T-Tubules in the Heart The entire depth of the cell can then contract together, even though the signal arrives only at its surface.15PubMed Central. The structure and function of cardiac t-tubules in health and disease
Released calcium attaches to the filaments and lets myosin grab actin. Pumps then pull calcium back into the store, and the cell relaxes before the next beat.
A small trigger releasing a big store lets the cell scale its squeeze, since a larger trigger can mean a stronger contraction. Because only a little enters per beat, the cell must remove that same amount each time, or it would slowly overload.
This is why so many heart drugs act on calcium channels, slowing or weakening the trigger step. Adrenaline makes the heart beat harder in part by boosting the calcium signal.
How Millions of Cells Beat as One
Heart cells connect end to end at a specialized junction that links them both mechanically and electrically.16PubMed Central. The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes Two kinds of anchoring joints there keep cells from pulling apart as they squeeze.17PubMed. Cardiac cell-cell junctions in health and disease: Electrical versus mechanical coupling A third kind, gap junctions, are small pores that let the electrical signal pass straight into the next cell.18PubMed. Cardiac cell-cell junctions in health and disease: Electrical versus mechanical coupling The signal spreads across the heart cell by cell, so the muscle contracts in a coordinated wave.19PubMed. Cardiac cell-cell junctions in health and disease: Electrical versus mechanical coupling
Without anchors, cells would tear apart under the force of each beat. Without gap junctions, each cell would beat on its own and the heart would quiver rather than pump. Damage to these joints is linked to inherited heart muscle diseases and rhythm problems.
The spread takes a small but real amount of time, so different parts of the heart contract in a sequence rather than at the exact same instant. That sequence helps push blood in the right direction through the chambers instead of squeezing it in all directions.
Along their sides, heart cells are also anchored to the supporting mesh around them at attachment points lined up with the contracting units.20PubMed Central. Cardiac mechanotransduction from development to disease The pull of each contraction is spread across the cell surface and into the surrounding tissue.21PubMed Central. Cardiac mechanotransduction from development to disease Other cells in the heart, such as connective tissue cells and the cells lining blood vessels, also connect to heart muscle cells and send them chemical signals.22PubMed Central. The Roles of Cardiac Fibroblasts and Endothelial Cells in Myocarditis
Pacemaker Cells and Other Types
A small group of pacemaker cells fires on its own to start every heartbeat. Their electrical signal is very different from that of the pumping cells in the lower chambers. Their calcium channels don’t stay open, so their signal lacks the long held phase the pumping cells have and rises and falls in a triangle shape.23TeachMePhysiology. Cardiac Pacemaker Cells – Cardiac Cycle
A pacemaker cell’s resting voltage drifts upward on its own until it reaches the point where it fires, so it needs no outside push. Ordinary pumping cells sit quietly at rest until a signal arrives from a neighbor. The current that helps pacemaker cells fire on their own barely exists in ordinary pumping cells.24PubMed. The cardiac pacemaker current When pumping cells make too much of it, as can happen in some diseases, it can cause irregular rhythms.25PubMed. The cardiac pacemaker current
The pumping cells’ long held phase keeps them contracting long enough to push blood out. It also stops a cell from being restarted too soon, which protects the rhythm. When natural pacemaker cells fail, an implanted pacemaker supplies the electrical spark, and the pumping cells still contract normally once the signal reaches them.
Working cells in the upper chambers (atria) and lower chambers (ventricles) switch on different genes for channels and structural proteins and behave differently.26PubMed. Differential gene expressions in atrial and ventricular myocytes: insights into the road of applying embryonic stem cell-derived cardiomyocytes for future therapies They even use different versions of some contraction proteins, which lets scientists tell the two types apart.27PubMed Central. Human iPSCs: atrial versus ventricular cardiomyocytes and their functional and pharmacological differences The atria contract first to top up the ventricles, which then deliver the main pump.
Why Heart Damage Is Mostly Permanent
The full set of heart muscle cells is in place around birth and stays roughly the same size for life.28PubMed. Dynamics of Cell Generation and Turnover in the Human Heart Some cells are still replaced: about 1% a year at age 20, slowing to about 0.3% a year by 75.29PubMed Central. Evidence for cardiomyocyte renewal in humans Fewer than half of your heart muscle cells are replaced over a normal lifetime.30PubMed Central. Evidence for cardiomyocyte renewal in humans Replacement is highest in early childhood.31PubMed. Dynamics of Cell Generation and Turnover in the Human Heart This slow trickle keeps pace with ordinary wear. It is not a repair system, and it is far too slow to refill a patch of muscle that dies all at once in a heart attack.
After birth, heart muscle cells largely lose the ability to divide, so damaged muscle fibers aren’t rebuilt.32Electronic Journal of General Medicine. Stem Cells and Myocardial Regeneration After a heart attack, lost muscle is replaced by scar tissue that doesn’t contract. Scar fills the gap so the wall does not burst, a real benefit in the first days and weeks. But scar does not squeeze or conduct the electrical signal the way muscle does, so the pump is weaker. The surviving muscle has to do extra work, which can strain it over time and contribute to heart failure.
Some animals do better. Adult zebrafish can fully regrow damaged heart muscle because their heart cells keep dividing.33PubMed Central. BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress In mice, switching off one gene that halts cell division after birth can make adult heart cells start dividing again.34PubMed Central. Mechanisms of Cardiac Regeneration Research on fish and mice aims to restart division in human cells, but no treatment does this yet.
What Goes Wrong in Heart Failure and Aging
In heart failure, a condition where the heart can’t pump as well as the body needs, the network of calcium tunnels inside cells becomes disorganized.35PubMed Central. Cardiomyocyte substructure reverts to an immature phenotype during heart failure Calcium is released more slowly and unevenly, and contractions are weaker.36PubMed Central. Cardiomyocyte substructure reverts to an immature phenotype during heart failure Because calcium arrives slowly and unevenly, the contracting units don’t all switch on together, so the cell produces less force even though its filaments are intact.
The disorganized tunnels resemble those of an immature heart cell, with fewer crosswise tunnels and more running lengthwise.37PubMed Central. Cardiomyocyte substructure reverts to an immature phenotype during heart failure Even where the calcium machinery looks normal, the contact points in failing cells work poorly.38PubMed Central. Cardiomyocyte substructure reverts to an immature phenotype during heart failure In an animal model, a treatment that resynchronizes the heartbeat with a special pacemaker restored the tunnels and contact points.39PubMed Central. Subcellular Structures and Function of Myocytes Impaired during Heart Failure are Restored by Cardiac Resynchronization Therapy
Fuel shows a similar pattern. The heart gets 60 to 70% of its energy from burning fat, which uses a lot of oxygen.40PubMed Central. Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets But a thickened, strained heart shifts toward using sugar and burns fat less, which looks like a return to the fuel pattern of a fetal heart.41PubMed Central. Cardiac Metabolism and Its Interactions with Contraction, Growth, and Survival of the Cardiomyocte Both the tunnels and the fuel choice resemble an earlier stage, which suggests failure partly undoes the cell’s normal maturing. Researchers see reversing that as a possible treatment target.
Strain itself is sensed by the cells. They detect stretch, such as from high blood pressure, through their anchoring points and stretch-sensitive channels.42PubMed Central. Cardiac mechanotransduction from development to disease These signals switch on genes that make cells grow larger and increase scarring.43PubMed Central. Cardiac mechanotransduction from development to disease This is one reason long-term high blood pressure thickens and eventually weakens the heart.
Age brings its own wear. Young heart cells quickly clear out damaged mitochondria before they cause harm.44PubMed Central. The impact of aging on cardiac repair and regeneration This cleanup slows with age, so damaged mitochondria pile up and release more harmful byproducts, which damages more of them.45PubMed Central. The impact of aging on cardiac repair and regeneration Aged, worn-out heart cells contract less, grow larger, accumulate, and trigger ongoing inflammation.46PubMed Central. Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets
Growing Heart Cells in the Lab
Ordinary adult cells, such as skin or connective tissue cells, can be reprogrammed into stem cells and then turned into beating heart cells. These lab-grown cells are less mature than adult ones, so scientists mimic conditions in a growing heart, such as stretch and electrical pacing, to mature them.47PubMed Central. Engineering the maturation of stem cell-derived cardiomyocytes Growing them in 3D tissue built from real heart scaffolding produces more mature, better-organized cells than flat dishes.48PubMed. Engineered heart tissue models from hiPSC-derived cardiomyocytes and cardiac ECM for disease modeling and drug testing applications
Maturity matters because immature cells contract more weakly and have less developed internal structure, so they behave less like an adult heart. That affects how they respond to drugs, and a test on immature cells may not match what happens in an adult heart.
One team seeded a 3D-printed scaffold with about 50,000 lab-grown heart and blood vessel cells to make a muscle patch.49PubMed Central. Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold The cells beat together across the whole patch within a day.50PubMed Central. Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold Over the next week the patch contracted and relaxed faster and its calcium signals grew stronger.51PubMed Central. Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold So far this has been tested in mice with heart injury, not as a routine human treatment.52PubMed Central. Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold Getting patches to survive, wire in, and beat in step with a human heart remains a hurdle, and any clinic offering stem cell heart repair today is outside proven medicine.
Lab-grown heart cells and cloned channels let drug makers check whether a medicine disrupts the heart’s electrical channels.53PubMed Central. New in vitro multiple cardiac ion channel screening system for preclinical Torsades de Pointes risk prediction under the Comprehensive in vitro Proarrhythmia Assay concepta For example, the heart drug sotalol blocks one key channel strongly at high levels, while mexiletine barely affects it.54PubMed Central. New in vitro multiple cardiac ion channel screening system for preclinical Torsades de Pointes risk prediction under the Comprehensive in vitro Proarrhythmia Assay concepta Screening like this helps catch drugs that might cause dangerous rhythms before they reach patients.
The cells are also useful for studying disease. Cells from a patient with an inherited heart condition can be turned into heart cells carrying the same genes. Researchers can then watch the disease and test medicines on that person’s own cells. These cells beat and respond to drugs like heart cells, which makes them good test models, even though they lack the full structure of adult cells, including well-developed calcium tunnels.