Intracellular Communication 101
The nervous system is one of the major control centers of the body. It is composed of sensory receptors and nerve tracts, which bring information about the body (internal and external) to the brain. The brain processes the information and determines how to respond. Those responses leave the brain via different nerve tracts, travel through the spinal cord, and are dispersed through nerves to the appropriate target, such as different tissues. All of this information is moved around the body via ions and chemicals in and around the nerve cells. Therefore, the signal transduction of information is essential for the nervous system.
Signal Transduction
As discussed earlier, neurons use their plasma membrane to selectively concentrate ions in either the cytoplasm or outside of the cell, which affects the voltage of the membrane. When cells are inactive (at rest), the metabolic machinery of the cell works to create an appropriate concentration of two critical ions: sodium and potassium. A membrane protein called the sodium-potassium pump (Na/K pump) uses energy to move sodium outside of the cell, while at the same time moving potassium inside. This, as well as the number of fixed charged particles on the inside of the cell (such as DNA and charged proteins of the cytoskeleton), results in the interior of the cell being more positive than the outside of the cell, creating a membrane voltage of approximately −70 mV (a millivolt, mV, is one-thousandth of a volt). Since the cell is at rest, this voltage is termed the resting membrane potential.
Voltage-Gated Receptors
When stimulated, protein receptors cause some ions to diffuse out of their compartment and alter the membrane voltage. If this change is of sufficient magnitude, some membrane proteins actually change their shape. These shape-changing proteins are said to be “voltage-gated” channels. For instance, one such channel will change shape at a voltage of −56 mV in such a way as to allow sodium ions to diffuse into the cell. Since sodium is positively charged, this causes the membrane voltage to become more positive and possibly affect other voltage-gated channels that respond at different voltages. Potassium voltage-gated channels open when the membrane potential is in the positive range.
Action Potential
The process of channels opening and closing and ions changing place creates a wave of voltage changes that can affect nearby areas of the membrane, causing them to undergo the same changes. This wave of voltage changes moves along the axon of a nerve cell in much the same way that the wave moves in the stands at a football game. In the stadium, as a person stands up then sits, the next person knows to then stand and sit, and so on.
On the cell membrane, sodium channels open at −56 mV and the movement of sodium causes the membrane potential to become more positive (and move toward 0 mV). This change is called depolarization of the membrane. Because sodium flows into the cell more rapidly than needed, the sodium channel inactivates quickly after it opens to prevent too much sodium from coming in. However, this still allows enough sodium in to change the membrane potential into the +30 mV range. Inactivation is different from the channel being closed, which occurs more slowly. Inactivation means that although the shape of the channel remains the same, another part of the protein has moved into place to block the passage of any further ions until the entire protein can reset and close.
As sodium rushes into the cell, it disperses throughout the cell, leading to an increase of the membrane potential in the area of neighboring sodium voltage-gated channels, which are still closed. This leads to the neighboring sodium channels opening if the membrane potential in that area also reaches −56 mV. This will continue the length of the axon as long as there are sodium voltage-gated channels to be opened.
When the membrane potential enters the positive realm, potassium voltage-gated channels open and potassium rushes out of the cell by diffusion. Since potassium is positive, the potential becomes more negative, therefore repolarizing the membrane. As with the sodium channels, the potassium channels open and inactivate quickly, but not fast enough to prevent the potential from becoming even more negative than the resting membrane potential of −70 mV. This period is termed hyperpolarization, and although the voltage has returned to that near resting potential, the concentration of sodium and potassium ions has been reduced. To reset the ion concentrations, the Na/K pump shifts into high gear to pump sodium out and potassium in to re-create the high concentration gradients sufficient to have another action potential occur in the area of the cell.
Neurotransmitters
Action potential works very well to transmit electrical signals within a cell. However, these electrical signals cannot move across space and continue in an adjacent cell spontaneously. Thus, to functionally interconnect neurons with each other and to their target tissues, the electrical signals are transduced (changed) into chemical messengers that can be secreted, diffused through space, and be detected by the receiving cell that can transduce the now chemical signal back into an electrical action potential.
Types of neurotransmitters
Neurotransmitters are the chemical messengers of the nervous system. Several different types of these molecules function with different tissues, are secreted by specific neurons, and elicit prescribed effects from the target tissues:
· Acetylcholine (ACh) is the neurotransmitter most commonly secreted from motor neurons. Because of the interaction with ACh and its receptor, the result is always an increase in the membrane potential of the receiving cell. Therefore, ACh is said to always be excitatory in nature.
· Norepinephrine affects smooth and cardiac muscle as well as glands of the body. Norepinephrine belongs to a group of neurotransmitters called catecholamines (molecules derived from the amino acid tyrosine), and functions largely in the involuntary nervous system to control those body functions either during rest or in fight-or-flight mode.
· Other neurotransmitters, such as dopamine, serotonin, and gamma amino butyric acid (GABA), are found in the brain and control hunger, behavior, mood, and overall brain activity.
Chemically Gated Receptors
Without a receptor to detect and instruct the cell, neuro-transmitters would have no effect. Thus, the receptors are equally as important as the neurotransmitters themselves.
On skeletal muscle cells, the ACh receptor (nicotinic ACh receptor) binds to 2 molecules of ACh, changing the shape of the receptor. This opens a channel in the protein through which sodium and potassium can diffuse, resulting in a positive change in the membrane potential. Since these are chemically gated responses, the process is not referred to as a depolarization; rather, it is called an excitatory potential.
Smooth and cardiac muscles have a different ACh receptor, the muscarinic type. Binding of a single ACh molecule leads to a shape change in this protein, but it is not an ion channel as with the nicotinic receptor. The shape change leads to a signaling cascade of molecules, much like a series of dominoes knocking each other over, that ends in either opening or closing the ion channels. Depending on the ion and the directional effect, this type of signaling is either excitatory or inhibitory (decreasing the membrane potential).
Receptors for other neurotransmitters in other tissues similarly transduce signals and lead to alterations in their membrane potentials and yield an appropriate physiological response.
Synapse
When the end of a nerve cell (the axon terminal) approaches the target tissue, such as a skeletal muscle cell, a space is created between the membranes of each cell (the synaptic cleft). When released from the axon terminal, neurotransmitters diffuse across this space. Being on the receiving end of the chemical messages, the skeletal muscle cell membrane and its receptors are said to be part of the post-synaptic cell or membrane. As previously described, voltage-gated channels open and the action potential is regenerated in the new cell using the same machinery.