Ion Channels Within the cell membrane of all body cells are integral proteins, some of which contain watery pores through which ions (cations +, and anions -) may pass. Ion channels may be: 1. Selective: each ion channel typically allows only one ion to pass through. There are channels for Na+ and K+ within the cell membrane. 2. Gated or nongated: If an ion channel is nongated, it is always open and the ions are allowed to flow through the channel, usually based on some sort of gradient, typically along a chemical or electrical gradient, or both (electrochemical gradient). Gated channels are always closed until something opens them, usually when a chemical binds to a receptor site on the chemically gated channels, or when the voltage of the membrane changes, as with the voltage gated channels. 3. Functionally unique: The functions of the gated and nongated channels are different, but both are necessary for a resting membrane potential, and a subsequent action potential. Nongated channels establish a resting membrane potential. Chemically gated channels are necessary to receive the incoming stimulus, to initiate a depolarization and action potential. Voltage gated channels are responsible for the generation and propagation of an action potential. Resting Membrane Potential In order for a cell to receive a stimulus and to respond to that stimulus, a cell must have a resting membrane potential, or a separation of electrical charges across the cell membrane, with positive charges predominating along the outside face of the cell membrane, and negative charges predominating along the inside face of the cell membrane. However, one must keep in mind that there is an equal amount of positive and negative charges inside and outside of the cell, to keep the body electrically neutral. It’s just that at the cell membrane, positive charges tend to collect outside of the membrane and negative charges collect on the inside of the membrane. In addition to a separation of charges across a membrane, there is also a separation of ions across the membrane, due to the selectivity of the ion channels. Na+ is the predominant extracellular cation. Its positive charge is balanced by the abundance of Cl- ions extracellularly. Within the cell, there is an abundance of negatively charged proteins and anions, which are balanced by K+ ions, the predominant intracellular cation. The movement of these ions through nongated channels is necessary to establish a membrane potential. The following steps outline the development of this potential. How to establish a membrane potential: 1. K+ tends to travel down its concentration gradient from inside of the cell to the outside of the cell through nongated K+ channels. This produces a chemical force out of the cell. 2. As K+ leaves the cell, the anions make the inside of the cell membrane more negative and the outside more positive. 3. Some of the K+ is drawn back into the cell due to the negative charge inside the cell membrane. This produces an electrical force back into the cell. 4. But when the chemical and electrical forces on K+ are equal, the resulting membrane potential (or the inside of the cell) is equal to -90 mV. 5. But K+ is not the only ion to which a cell membrane is permeable. The greater Na+ concentration outside the cell and the negative charge of the inner membrane both draw Na+ into the cell. This addition of another cation causes the resting membrane potential to become -70 mV. 6. However, K+ continually leaks out of the cell and Na+ continually leaks into the cell, risking an elimination of the membrane potential. This is prevented by the Na+/K+ pump, which pumps 3 Na+ out of the cell and 2K+ into the cell for every ATP molecule it uses. Action Potential Generation When a cell receives a stimulus, it needs to be able to pick up the stimulus and then respond. The following outline the steps to an action potential, or a wave of depolarization along the cell membrane. 1. A signal coming from a neuron, in the form of a neurotransmitter, binds to a receptor on a chemically gated Na+ channel. This causes the channel to open, allowing Na+ to rush into the cell. At the site of the chemically gated Na+ channel, the influx of Na+ ions, due to the electrochemical gradient for Na+, causes the inside of the membrane to become less negative, and the outside of the membrane to become more negative. This reversal of charges is called DEPOLARIZATION. 2. When the inside of the membrane depolarizes to -55 mV, the voltage gated Na+ and K+ channels open. A stimulus that takes the membrane to -55 mV or more is known as a THRESHOLD STIMULUS. The voltage gated Na+ channels are sensitive to both charge and time. As a threshold stimulus occurs, Na+ rushes into the cell, depolarizing yet another portion of the cell membrane. This, in turn, will open other adjacent voltage gated channels all the way down the cell membrane in all directions. This positive feedback, or wave of depolarization is known as an ACTION POTENTIAL. But as soon as the voltage gated Na+ channels open, they immediately close. 3. The action potential causes the inside of the membrane to reach +30 mV. By the time that this value is reached, the voltage gated Na+ channels are closed and the slow-to-open voltage gated K+ channels are open, ending the positive feedback loop. Repolarization In order for a cell to be able to respond to another incoming signal, it must return to its original resting membrane potential. Since the voltage gated Na+ channels are now closed, they cannot be responsible for this. This is the role of voltage gated K+ channels. 1. When the voltage gated K+ channels slowly open, K+ rushes out of the cell, due to its electrochemical gradient. This makes the membrane increasingly more negative on the inside, and eventually the resting membrane potential returns to the original -70 mV, with the inside face of the membrane returning to a negative state, and the outside face of the cell membrane becoming positive again. This is called REPOLARIZATION. 2. This can continue for quite a long period of time, since there is little Na+ and K+ required for depolarization and repolarization of the membrane. However, since the Na+/K+ pump is always working, after a stimulus and action potential have passed, the pump can return the ions back to their original concentrations inside and outside of the cell.