How Neurons work.

Neuron Membrane (Resting) Potential

Like all living cells, neurons develop and maintain a electric potential across the cell membrane—a membrane potential.  An electric potential is basically the separation of two charges--just like the two parts of a battery. Positive and negative charges attract each other. Keeping them separated then is a form of potential energy--if we let them go they will come together. A membrane potential is the same concept; there is just the membrane of a living cell that is keeping the charges separated.  

We measure the strength of an electric potential in volts. The more volts, the greater the attraction between the unlike charges. So we have 1.5V batteries, 12V batteries, 110V electric lines, etc.  In the case of cells, we use millivolts (thousandths of a volt) as the unit of measure. In the normal resting state, the inside of the neuron is more negative than the outside. If measured with microelectrodes, the membrane potential is about -65mV.  

            If we are going to have a separation of charges between the inside and outside of a cell, we need to have some charged particles. Fortunately, living cells have a wide variety of charged particles--ions.  In the case of neurons, there are four ions that are particularly important:  Na+, K+, Cl-, and A-.  A stands for anions; these are usually large organic molecules such as proteins within the cell which are unable to pass through the membrane. Due to the hydrophobic nature of the interior of the cell membrane, none of the other three ions can easily pass through the membrane without a transport protein facilitating their movement. Notice, however, that I said they can’t "easily" pass through--some do leak through the membrane, especially when there is large concentration difference. The -65mV potential occurs when most of the Na+ ions are moved out of the cell. There is a high concentration of K+ inside the cell. However, the A- ions cannot move at all. The net result is that the inside of the cell is negative. As Na+ and K+ ions leak through the membrane, there is a protein pump that puts them back where they belong. The pump is called the sodium/potassium pump and it uses ATP to move 3 Na+ and two K+ ions into the cell with each cycle. The end result that one positive charge is removed from the cell.  Here is animation on Sodium-Potassium Exchange  

Keep in mind that neurons are continually pumping ions even when there is no nerve transmission activity occurring. They require large amounts of ATP (hence oxygen) continually to maintain the membrane (resting) potential. 

Questions to check understanding. 

a. List the ions involved in developing this membrane potential (i.e., which ions are at a higher concentration outside the cell than inside and vice versa).

b. Since the ions are at different concentrations inside and outside the cell membrane, something must happen to separate them and keep them separated. What active process does the cell use to make this happen? What role does the cell membrane play in this process? 

c. Starting with a cell in which all the ions involved in a membrane potential are at equal concentrations on both sides of the cell membrane, describe the sequence of events that leads to a full membrane potential.

    Now that we have established a membrane potential, the only way to transmit information is by changes in the membrane potential; if there no changes, there is no way to pass information (think about it). The change in potential used to transmit information is called an action potential. An action potential is a transient (temporary) change in the electrical charge of the cell; then the cell returns to the normal membrane potential. A stimulation of the membrane, if it a strong enough stimulus, will cause a change in the properties of the cell membrane that will allow a movement of ions--creation of an action potential. The ions are able to move because there are voltage "gates" in the membrane that are specific for Na+ and K+ ions respectively. These gates open and close to allow movement of ions.  

            Keeping in mind that this entire activity is occurring at a molecular sized spot on the membrane at the base of the axon--the axon hillock. When the cell receives sufficient stimulation to lower the membrane potential enough to respond, the Na+ voltage gate opens. Since there is a high concentration of Na+ outside the cell and there is now an opening in the membrane, Na+ ions flood into the cell. The inside of the cell becomes less negative and actually becomes positive (it spikes at about +40 mV). This part of the process is called depolarization because the original polarization of the membrane (negative inside) is lost.  

            At this point the Na+ gate closes and the inside of the cell is at its maximum positive value. The K+ gate opens and K+ ions begin to leave the cell--positive charges repel and the cell is now full of Na+ ions that can’t get out--their gate is closed. As K+ ions leave, the inside of the cell becomes less positive and eventually returns to a -65 mV. This part of the process is called repolarization. The K+ gate now closes and the cell has returned to its original membrane potential--except that the ions are now on the wrong side of the membrane. To return the neuron to its original configuration, the sodium/potassium pumps which have been working continuously return the Na+ to the outside of the membrane and bring K+back inside. This entire process take approximately 15 milliseconds--15 thousandths of one second.   

            There are three Principles that characterize the action potential: 

1. There is a threshold that must be reached before the process starts. If the stimulus is not sufficient, there will be no response. Think of a mouse trap. If the mouse touches the bait but does not apply sufficient force to trigger the trap, noting happens. This concept means that there can be stimuli below the threshold that the nervous system will not detect. 

2. It is an all-or-nothing event. Once the process begins, it cannot be stopped in mid ion stream. There are not different sized action potentials; they are all the same size. They either occur completely or they do not occur at all. Once the mouse trap is triggered, the trap springs all the way shut. You will not find a mouse trap half way shut. 

3. There is a refractory period during which the cell cannot respond. This is the time period from when the stimulus first triggered the response until the action potential is finished and the membrane potential is reestablished. Once this process begins, the cell cannot respond again until it is completed--this is the 15 millisecond time period. Returning to the mouse trap example, once the trap snaps shut, it can’t close again until it is reset. 

            Returning to our action potential at that molecular sized spot on the membrane, it is useless unless the depolarization process moves along the axon membrane to the end of the axon. This process is called nerve conduction. The depolarization at one point on the membrane induces the voltage gate next to that spot to open beginning a depolarization process at that next point. This depolarization induces the next voltage gate to open, etc. It is like pushing one domino over and then watching each domino fall into the next one, then the next, until we reach the end of the line (axon). If the nerve axon has a myelin sheath, the depolarization jumps from node to node along the axon, resulting in faster nerve conduction. This process is much like an express train skipping stations and getting to the end of the line sooner than the local train that stops at every station. 

Questions to check understanding.

a. When a strong enough stimulus reaches the cell, describe what happens to the Na+ ion gate. 

b. Describe what happens to the K+ ion gate. 

c. How would the resting potential be reestablished following an action potential?