In physiology, a refractory period is a period of time during which an organ or cell is incapable of repeating a particular action, or (more precisely) the amount of time it takes for an excitable membrane to be ready for a second stimulus once it returns to its resting state following an excitation. It most commonly refers to electrically excitable muscle cells or neurons. This term is similarly used in psychological terms: it is defined as the time it takes for a neuron to repolarize so it can fire again.

Electrochemical usage

''See also: Action potential

After initiation of an action potential, the refractory period is defined two ways:

• The absolute refractory period is the interval during which a second action potential absolutely cannot be initiated, no matter how large a stimulus is applied.
• The relative refractory period is the interval immediately following during which initiation of a second action potential is inhibited but not impossible.

The absolute refractory period coincides with nearly the entire duration of the action potential. In neurons, it is caused by the inactivation of the Na⁺ channels that originally opened to depolarize the membrane. These channels remain inactivated until the membrane repolarizes, after which they close, reactivate and regain their ability to open in response to stimulus.

The relative refractory period immediately follows the absolute. As voltage-gated potassium channels open to terminate the action potential by repolarizing the membrane, the potassium conductance of the membrane increases dramatically. K⁺ ions flooding out of the cell bring the membrane potential closer to the equilibrium potential for potassium. This causes brief hyperpolarization of the membrane, that is, the membrane potential becomes transiently more negative than the normal resting potential. Until the potassium conductance returns to the resting value, a greater stimulus will be required to reach the initiation threshold for a second depolarization. The return to the equilibrium resting potential marks the end of the relative refractory period.

Cardiac refractory period

The refractory period in cardiac physiology is related to the ion currents which, in cardiac cells as in nerve cells, flow into and out of the cell freely. The flow of ions translates into a change in the voltage of the inside of the cell relative to the extracellular space. As in nerve cells, this characteristic change in voltage is referred to as an action potential. Unlike nerve cells, the cardiac action potential duration is closer to 100 ms (with variations depending on cell type, autonomic tone, etc.). After an action potential initiates, the cardiac cell is unable to initiate another action potential for some duration of time (which is slightly shorter than the "true" action potential duration). This period of time is referred to as the refractory period.

Classically, the cardiac refractory period is separated into an absolute refractory period and a relative refractory period. During the absolute refractory period, a new action potential cannot be elicited. During the relative refractory period, a new action potential can be elicited under the correct circumstances.

Neuronal refractory period

The refractory period in a neuron occurs after an action potential and generally lasts one millisecond. An action potential consists of three phases. Phase one is depolarization. During depolarization, voltage-gated sodium ion channels open increasing the neuron's membrane conductance for sodium ions and depolarizing the cell's membrane potential (from typ. -70mV towards a positive potential). In other words, the membrane is made less negative. After the potential reaches the activation threshold (-55mV) the depolarisation is actively driven by the neuron and overshoots the equilibrium potential of an activated membrane (+50mV). Phase two is repolarization. During repolarization, voltage-gated sodium ion channels inactivate (different than the close state) due to the now depolarized membrane, and voltage-gated potassium channels activate (open). Both the sodium ion channels closing and the potassium ion channels opening act to repolarize the cell's membrane potential back to its resting membrane potential. When the cell's membrane voltage overshoots its resting membrane potential (near -60mV), the cell enters a phase of hyperpolarization. This is due to a larger than resting potassium conductance across the cell membrane. Eventually this potassium conductance drops and the cell returns to its resting membrane potential.

The refractory periods are due to the inactivation property of voltage-gated sodium channel and the lag of potassium channels in closing. Voltage-gated sodium channels have two gating mechanisms, one that opens the channel with depolarization and the inactivation mechanism that closes the channel with repolarization. While the channel is in the inactive state it will not open in response to depolarization. The period when the majority of sodium channels remain in the inactive state is the absolute refractory period. After this period there are enough voltage-activated sodium channels in the closed (active) state to respond to depolarization. However, voltage gated potassium channels that opened in response to depolarization don't close as quickly as voltage gated sodium channels return to the active closed state. During this time the extra potassium conductance means that the membrane is at a lower threshold and will require a greater stimulus to cause action potentials to fire. This period is the relative refractory period.

Sexual refractory period

In sexual intercourse, the refractory period is a recovery phase after orgasm during which it is physiologically impossible and painful for a person to experience continued arousal or additional orgasms. Parts of the vagina or penis may become hypersensitive and further sexual stimulation may even feel painful during this time frame.

The refractory period varies widely among individuals and across species, ranging from nonexistent to hours. An increased infusion of the hormone prolactin (which represses dopamine, which is responsible for sexual arousal) during orgasm is believed to be chiefly responsible for the refractory period and the amount by which prolactin is increased may affect the length of each refractory period.

Another chemical which is considered to be responsible for this effect is oxytocin, although, as oxytocin has a half-life of typically about three minutes in the blood, it would not create a long-term refractory period.

Some people do not experience a refractory period immediately after orgasm and in many cases are capable of attaining additional, multiple orgasms through further stimulation. The female sexual response is more similar to that of men than previously thought. Most men and women experience hypersensitivity after orgasm, which effectively creates a refractory period. During a refractory period it may be difficult to be aroused by physical stimulation alone, but an element of mental stimulation may help reinstate arousal.

In males of some species, reaching orgasm increases the levels of prolactin, which repress the arousal properties of dopamine. In some men who reach orgasm quickly or suppress orgasm, not enough dopamine may be built up to experience as satisfactory an orgasm as desired, and the likelihood of a refractory period is increased.