Active cell and Active transport

 Electrically active cells such as neural cells or muscle cells generate small currents in short spikes, which are called action potentials. These currents are actually due to ions (Na+, K+) moving across the cell membrane through protein channels. Extracellular recording from close proximity to cells can pick up these signals which ranges 100–1000 µV.

Electrochemical gradient exists whenever there is a net difference in charges. The positive and negative charges of a cell are separated by a membrane, where the inside of the cell has extra negative charges than outside. The membrane potential of a cell is -40 to -80 millivolts.

The cell has higher potassium concentration inside the cell but lower sodium concentration than the extracellular fluid. The sodium ions will move inside the cell based on the concentration gradient and voltage across the membrane. The voltage across the membrane facilitates the movement of potassium into the cell, but its concentration gradient drives it out of the cell. The combination of voltage across the membrane and the concentration gradient that facilitates the movement of ions is called the electrochemical gradient.

Active transport is essential for various physiological processes, such as nutrient uptake, hormone secretion, and nerve impulse transmission.

For example, the sodium-potassium pump uses ATP to pump sodium ions out of the cell and potassium ions into the cell, maintaining a concentration gradient essential for cellular function. Active transport is highly selective and regulated, with different transporters specific to different molecules or ions. Dysregulation of active transport can lead to various disorders, including cystic fibrosis, caused by a malfunctioning chloride channel, and diabetes, resulting from defects in glucose transport into cells.

Active transport is usually associated with accumulating high concentrations of molecules that the cell needs, such as ions, glucose and amino acids. Examples of active transport include the uptake of glucose in the intestines in humans.

the sodium-calcium exchanger or antiporter, which allows three sodium ions into the cell to transport one calcium out.^[24] This antiporter mechanism is important within the membranes of cardiac muscle cells in order to keep the calcium concentration in the cytoplasm low.^[9] Many cells also possess calcium ATPases, which can operate at lower intracellular concentrations of calcium and sets the normal or resting concentration of this important second messenger.

An example is the glucose symporter SGLT1, which co-transports one glucose (or galactose) molecule into the cell for every two sodium ions it imports into the cell.^[27] This symporter is located in the small intestines,^[28] heart,^[29] and brain.^[30] It is also located in the S3 segment of the proximal tubule in each nephron in the kidneys.^[31]

Na⁺/Ca²⁺ exchanger in the cardiac action potential[edit]

The ability for the Na⁺/Ca²⁺ exchanger to reverse direction of flow manifests itself during the cardiac action potential. Due to the delicate role that Ca²⁺ plays in the contraction of heart muscles, the cellular concentration of Ca²⁺ is carefully controlled. During the resting potential, the Na⁺/Ca²⁺ exchanger takes advantage of the large extracellular Na+ concentration gradient to help pump Ca²⁺ out of the cell.^[12] In fact, the Na⁺/Ca²⁺ exchanger is in the Ca²⁺ efflux position most of the time. However, during the upstroke of the cardiac action potential there is a large influx of Na⁺ ions. This depolarizes the cell and shifts the membrane potential in the positive direction. What results is a large increase in intracellular [Na⁺]. This causes the reversal of the Na⁺/Ca²⁺ exchanger to pump Na⁺ ions out of the cell and Ca²⁺ ions into the cell.^[12] However, this reversal of the exchanger lasts only momentarily due to the internal rise in [Ca²⁺] as a result of the influx of Ca²⁺ through the L-type calcium channel, and the exchanger returns to its forward direction of flow, pumping Ca²⁺ out of the cell.^[12]

While the exchanger normally works in the Ca²⁺ efflux position (with the exception of early in the action potential), certain conditions can abnormally switch the exchanger to the reverse (Ca²⁺ influx, Na⁺ efflux) position. Listed below are several cellular and pharmaceutical conditions in which this happens.^[12]

In the example of Na⁺, both terms tend to support transport: the negative electric potential inside the cell attracts the positive ion and since Na⁺ is concentrated outside the cell, osmosis supports diffusion through the Na⁺ channel into the cell. In the case of K⁺, the effect of osmosis is reversed: although external ions are attracted by the negative intracellular potential, entropy seeks to diffuse the ions already concentrated inside the cell. The converse phenomenon (osmosis supports transport, electric potential opposes it) can be achieved for Na⁺ in cells with abnormal transmembrane potentials: at +70 mV, the Na⁺ influx halts; at higher potentials, it becomes an efflux.

Biological context[edit]

The generation of a transmembrane electrical potential through ion movement across a cell membrane drives biological processes like nerve conduction, muscle contraction, hormone secretion, and sensation. By convention, physiological voltages are measured relative to the extracellular region; a typical animal cell has an internal electrical potential of (−70)–(−50) mV.^[2]: 464

Similar to skeletal muscle, the resting membrane potential (voltage when the cell is not electrically excited) of ventricular cells is around −90 millivolts (mV; 1 mV = 0.001 V), i.e. the inside of the membrane is more negative than the outside. The main ions found outside the cell at rest are sodium (Na⁺), and chloride (Cl⁻), whereas inside the cell it is mainly potassium (K⁺).^[7]

This phase is also known as the "plateau" phase due to the membrane potential remaining almost constant, as the membrane slowly begins to repolarize. This is due to the near balance of charge moving into and out of the cell. During this phase delayed rectifier potassium channels (I_ks) allow potassium to leave the cell while L-type calcium channels (activated by the influx of sodium during phase 0) allow the movement of calcium ions into the cell. These calcium ions bind to and open more calcium channels (called ryanodine receptors) located on the sarcoplasmic reticulum within the cell, allowing the flow of calcium out of the SR. These calcium ions are responsible for the contraction of the heart.

Calcium also activates chloride channels called I_to2, which allow Cl⁻ to enter the cell. Increased calcium concentration in the cell also increases activity of the sodium-calcium exchangers, while increased sodium concentration (from the depolarisation of phase 0) increases activity of the sodium-potassium pumps. The movement of all these ions results in the membrane potential remaining relatively constant, with K⁺ outflux, Cl⁻ influx as well as Na⁺/K⁺ pumps contributing to repolarisation and Ca²⁺ influx as well as Na⁺/Ca²⁺ exchangers contributing to depolarisation.^[22][12] This phase is responsible for the large duration of the action potential and is important in preventing irregular heartbeat (cardiac arrhythmia).

There is no plateau phase present in pacemaker action potentials.

Phase 3[edit]

During phase 3 (the "rapid repolarization" phase) of the action potential, the L-type Ca²⁺ channels close, while the slow delayed rectifier (I_Ks) K⁺ channels remain open as more potassium leak channels open. This ensures a net outward positive current, corresponding to negative change in membrane potential, thus allowing more types of K⁺ channels to open. These are primarily the rapid delayed rectifier K⁺ channels (I_Kr) and the inwardly rectifying K⁺ current, I_K1. This net outward, positive current (equal to loss of positive charge from the cell) causes the cell to repolarize. The delayed rectifier K⁺ channels close when the membrane potential is restored to about -85 to -90 mV, while I_K1 remains conducting throughout phase 4, which helps to set the resting membrane potential^[23]

Ionic pumps as discussed above, like the sodium-calcium exchanger and the sodium-potassium pump restore ion concentrations back to balanced states pre-action potential. This means that the intracellular calcium is pumped out, which was responsible for cardiac myocyte contraction. Once this is lost, the contraction stops and the heart muscles relax.

In the sinoatrial node, this phase is also due to the closure of the L-type calcium channels, preventing inward flux of Ca²⁺ and the opening of the rapid delayed rectifier potassium channels (I_Kr).^[24]

The Goldman–Hodgkin–Katz voltage equation, sometimes called the Goldman equation, is used in cell membrane physiology to determine the reversal potential across a cell's membrane, taking into account all of the ions that are permeant through that membrane.