Phases Of The Cardiac Action Potential

The beating of the heart is probably associated with the phenomenon of life more strongly than any other single concept or process, both medically and metaphorically. When people discuss inanimate objects or even abstract concepts, they use terms such as "Her election campaign still has a pulse" and "The team's chances flat-lined when it lost its star player" to describe whether the thing in question is "alive" or not. And when emergency medical personnel come across a fallen victim, the first thing they check for is whether the victim has a pulse.

The reason a heart beats is simple: electricity. Like so many things in the biology world, however, the precise and coordinated way that electrical activity powers the heart to pump vital blood toward the body's tissues, 70 or so times a minute, 100,000 times a day for decades on end, is wondrously elegant in its operation. It all starts with something called an action potential, in this case a cardiac action potential. Physiologists have divided this event into four distinct phases.

Cell membranes have what is known as an electrochemical gradient across the phospholipid bilayer of the membrane. This gradient is maintained by protein "pumps" embedded in the membrane that move some types of ions (charged particles) across the membrane in one direction while similar "pumps" move other types of ions in the opposite direction, leading to a situation in which charged particles "want" to flow in one direction after being shuttled in the other, like a ball that keeps "wanting" to return to you as you repeatedly toss it straight into the air. These ions include sodium (Na⁺), potassium (K⁺) and calcium (Ca²⁺). A calcium ion has a net positive charge of two units, twice that of either a sodium ion or a potassium ion.

To gain a sense of how this gradient is maintained, imagine a situation in which dogs in a playpen are moved in one direction across a fence while goats in an adjacent pen are carried in the other, with each type of animal intent on getting back to the spot in which it started. If three goats are moved into the dog zone for every two dogs moved into the goat zone, then whoever is responsible for this is maintaining a mammal imbalance across the fence that is constant over time. The goats and dogs that try to return to their preferred spots are "pumped" outside on a continuous basis. This analogy is imperfect, but offers a basic explanation of how cell membranes maintain an electrochemical gradient, also called a membrane potential. As you will see, the primary ions participating in this scheme are sodium and potassium.

An action potential is a reversible change of this membrane potential resulting from a "ripple effect" – an activation of currents generated by the sudden diffusion of ions across the membrane lowers the electrochemical gradient. In other words, certain conditions can disrupt the steady-state membrane ion imbalance and allow ions to flow in large numbers in the direction they "want" to go – in other words, against the pump. This leads to an action potential moving along a nerve cell (also called a neuron) or cardiac cell in the same general way a wave will travel along a string held almost taut at both ends if one end is "flicked."

Because the membrane usually carries a charge gradient, it is considered polarized, meaning characterized by different extremes (more negatively charged on one side, more positively charged on the other). An action potential is triggered by depolarization, which translates loosely to a temporary canceling out of the normal charge imbalance, or a restoration of equilibrium.

There are five cardiac action potential phases, numbered 0 through 4 (scientists get strange ideas sometimes).

Phase 0 is depolarization of the membrane and the opening of "fast" (i.e., high-flow) sodium channels. Potassium flow also decreases.

Phase 1 is partial repolarization of the membrane thanks to a rapid decrease in sodium-ion passage as the fast sodium channels close.

Phase 2 is the plateau phase, in which the movement of calcium ions out of the cell maintains depolarization. It gets its name because the electrical charge across the membrane changes very little in this phase.

Phase 3 is repolarization, as sodium and calcium channels close and membrane potential returns to its baseline level.

Phase 4 sees the membrane at its so-called resting potential of −90 millivolts (mV) as a result of the work of the Na+/K+ ion pump. The value is negative because the potential inside the cell is negative compared to the potential outside of it, and the latter is treated as the zero frame of reference. This is because three sodium ions are pumped out of the cell for every two potassium ions pumped into the cell; recall that these ions have an equivalent charge of +1, so this system results in a net efflux, or outflow, of positive charge.

So what does all of this ion-pumping and cell-membrane disruption actually lead to? Before describing how the electrical activity in the heart translates into heartbeats, it's helpful to examine the muscle that produces those beats itself.

Cardiac (heart) muscle is one of three kinds of muscle in the human body. The other two are skeletal muscle, which is under voluntary control (example: the biceps of your upper arms) and smooth muscle, which is not under conscious control (example: the muscles in the walls of your intestines that move digesting food along). All types of muscle share a number of similarities, but cardiac muscle cells have unique properties to serve the unique needs of their parent organ. For one thing, the initiation of the "beating" of the heart is controlled by special cardiac myocytes, or heart-muscle cells, called pacemaker cells. These cells control the pace of the heartbeat even in the absence of outside nerve input, a property called autorhythmicity. This means that even in the absence of input from the nervous system, the heart could in theory still beat as long as electrolytes (i.e., the aforementioned ions) were present. Of course, the pace of heart beat – also known as the pulse rate – does vary considerably, and this occurs thanks to differential input from a number of sources, including the sympathetic nervous system, the parasympathetic nervous system and hormones.

Heart muscle is also called myocardium. It comes in two types: myocardial contractile cells and myocardial conducting cells. As you may have surmised, the contractile cells do the work of pumping blood under the influence of the conducting cells that deliver the signal to contract. 99 percent of myocardial cells are of the contractile variety, and only 1 percent are dedicated to conduction. While this ratio rightly leaves most of the heart available to carry out work, it also means that a defect in the cells forming the cardiac conduction system can be difficult for the organ to circumvent using alternative conduction pathways, of which there are only so many. The conducting cells are generally much smaller than the contractile cells because they have no need for the various proteins involved in contraction; they need only be involved in faithful execution of the cardiac muscle action potential.

Phase 4 of the cardiac muscle cell potential is called the diastolic interval, because this period corresponds to diastole, or the interval between contractions of heart muscle. Every time you hear or feel the thump of your heartbeat, this is the end of the heart contracting, which as called systole. The faster your heart beats, the higher a fraction of its contraction-relaxation cycle it spends in systole, but even when you are exercising all-out and pushing your pulse rate into the 200 range, your heart is still in diastole most of the time, making phase 4 the longest phase of the cardiac action potential, which in total lasts about 300 milliseconds (three-tenths of a second). While an action potential is in progress, no other action potentials can be initiated in the same portion of cardiac cell membrane, which makes sense – once begun, a potential should be able to finish its job of stimulating a myocardial contraction.

As noted above, during phase 4, the electric potential across the membrane has a value of about −90 mV. This value applies to contractile cells; for conducting cells, it is closer to −60 mV. Clearly, this is not a stable equilibrium value or else the heart would simply never beat at all. Instead, if a signal lowers the negativity of the value across the contractile cell membrane to about −65 mV, this triggers changes in the membrane that facilitate sodium ion influx. This scenario represents a positive feedback system in that a disturbance of the membrane that pushes the cell in the direction of a positive charge value engenders changes that make the interior even more positive. With the rushing inward of sodium ions through these voltage-gated ion channels in the cell membrane, the myocyte enters phase 0, and the voltage level approaches its action-potential maximum of about +30 mV, representing a total voltage excursion from phase 4 of about 120 mV.

Phase 2 of the action potential is also called the plateau phase. Like phase 4, it represents a phase in which the voltage across the membrane is stable, or nearly so. Unlike the case in phase 4, however, this occurs in the phase of counterbalancing factors. The first of these consists of inward-flowing sodium (the influx which has not quite tapered to zero after the rapid influx in phase 0) and inward-flowing calcium; the other includes three types of outward rectifier currents (slow, intermediate and fast), all of which feature potassium movement. This rectifier current is what is ultimately responsible for the contraction of cardiac muscle, as this potassium efflux initiates a cascade in which calcium ions bind to active sites on cellular contractile proteins (e.g., actin, troponin) and cajole them into action.

Phase 2 ends when the inward flow of calcium and sodium cease while the outward flow of potassium (the rectifier current) continues, pushing the cell toward repolarization.

The cardiac cell action potential differs from the action potentials in nerves in a variety of ways. For one thing, and most importantly, it is much longer. This is essentially a safety factor: Because the cardiac cell action potential is longer, this means that the period in which a new action potential occurs, called the refractory period, is also longer. This is important, because it ensures a smoothly contacting heart even when it is operating at maximal speed. Ordinary muscle cells lack this property and can thus engage in what are called tetanic contractions, leading to cramping and the like. It is inconvenient when skeletal muscle behaves like this, but would be deadly if myocardium did the same.