in an electrolyte (salt solution) cause electrons to flow in an external circuit between two different electrodes that are immersed in the electrolyte.
You can think of neurons in the same way. In neurons, ions in solution such as sodium, potassium, or chloride move through specific channels in the membrane when these channels are opened by ligands or electric fields (voltage). The reasons for ions moving through membrane channels are diffusion (concentration differences between inside and outside) and voltage differences between the inside and outside. The continuous running of the transporter pumps maintains these concentration differences — or ionic imbalances.
Pumping Ions for Information
One of the most important kinds of molecular pumps are ion transporter pumps. These pumps use energy derived from adenosine triphosphate (ATP) to move specific ions through the membrane.
Sodium-potassium pump
One transporter pump is the sodium-potassium ATPase transporter. It creates a large imbalance between — you guessed it — the concentrations of sodium and potassium inside and outside the cell. It also causes the inside of neurons to be negatively charged inside versus outside, which is necessary for neurons to work.
The sodium-potassium ion pump or transporter is sometimes called an ion exchanger, because it works with two different ions.
The sodium-potassium pump pushes sodium ions outside the cell and potassium ions inside. The exchange ratio is three sodium ions pumped out for every two potassium ions pumped in. These pumps are ubiquitously expressed in neurons and run constantly. By always running, they create a disequilibrium or imbalance in sodium/potassium concentrations across the membrane, as you can see in Figure 3-1.
Figure 3-1: The sodium-potassium pump creates a disequilibrium between sodium and potassium concentrations inside versus outside the cell.
Here are two important facts about the sodium/potassium imbalance:
Compared to the extracellular fluid, which has high sodium and low potassium concentrations, the cell’s cytoplasm has almost the opposite: very low sodium and high potassium.
Because the sodium exit to potassium entry ratio is 3:2, a net loss of positive charge occurs inside the cell compared to outside. That is, neurons are negatively charged inside.
Because the negative potential inside neurons is based on the total difference in ionic concentrations between the inside and outside, if the transporter pumps stopped working and all other ion channels closed (in the impermeable state) a neuron’s resting potential (when nothing is passing through) would still exist for a long time. Scientists have done experiments to verify this, using poisons to kill the pumps and channel blockers to close all the ion channels.
Other important pumps
Besides the sodium-potassium ion pump, other transporters exist that are also essential for different aspects of neural function. One is the sodium-calcium exchanger. The main function of the sodium-calcium exchanger is to remove calcium from the cytoplasm. (Calcium levels inside cells are usually held to levels of a few hundred nanomolar.) The sodium-calcium exchanger is found not only in the plasma membranes, but also in mitochondria and the endoplasmic reticulum of neurons. The sodium-calcium exchanger works by using the energy stored in the electrochemical gradient of sodium instead of chemical energy from ATP. The energy derived from three sodium ions flowing down this gradient brings in one calcium ion.
Another important class of transporters is the group of cation chloride co-transporters (sometimes called CCCs). Variants of these exchangers may bring in or push out chloride in exchange for potassium or potassium and sodium. Membrane transporters also exist for neurotransmitters such as glutamate, dopamine, serotonin, and norepinephrine. These transporters are involved in limiting synaptic transmission by scavenging neurotransmitters from the synaptic cleft, thereby recycling the neurotransmitter molecules. (Chapter 4 gets into the processes involved in neurotransmitter release.) In some special cases, transporters can also release neurotransmitters.
Discovering Diffusion and Voltage
Ask any neurobiologist, and she’ll tell you that a big challenge in understanding the flow of currents through neural membranes is having to account for the two forces of imbalances: diffusion and voltage. Diffusion causes ions to move from regions of higher to lower concentration. As for voltage, the electrostatic force causes ions to move away from a like charge toward an opposite charge. Neurons have a net negative charge inside with respect to outside, and different concentrations of ions like sodium and potassium inside compared to outside. The following sections explore these ideas in more detail.
The upcoming sections look at how diffusion and electrostatic forces affect ion movement. Let’s look at the forces influencing sodium ions as an example. The sodium concentration is very low inside compared to outside the cell. The inside of the cell is also negatively charged. So, when membrane ion channels that are permeable to sodium open, the concentration gradient pushes sodium from its high concentration outside into the cell. Similarly, the electrostatic force (voltage) will also draw the positively charged sodium from outside to the negatively charged inside. Opening sodium channels will cause a large sodium inrush from both diffusion and the electrostatic force.
What about potassium? Potassium has a higher concentration inside than out, so diffusion tends to move it outside if potassium channels are opened. On the other hand, the negative charge inside the cell attracts positively charged potassium, just like it does sodium.
The Nernst equation
So, which way will potassium ions move if potassium channels are opened? The Nernst equation — developed from basic thermodynamic principles by the 19th-century German chemist Walter Nernst — gives us the answer. It gives the “balance point” (called the equilibrium potential) between the diffusion and voltage forces, expressed in terms of voltage. This equilibrium potential (sometimes called the Nernst potential, for obvious reasons) is the voltage (inside the cell versus outside) that would exactly balance the tendency of ions to diffuse down their concentration gradient. In other words, if the inside of the neuron is at the Nernst potential for an ion, no net movement of that ion will occur when the relevant channels are open.
A separate Nernst equation is written for each ion. The Nernst equation giving the equilibrium potential for sodium, ENa, would be written as follows:
in an electrolyte (salt solution) cause electrons to flow in an external circuit between two different electrodes that are immersed in the electrolyte.
