Cell Membrane, Channels and Receptors
Neurons are visually analogous to a tree with buds. In fact, the visual correspondence is so striking that the terms used by scientists for the growth of neurons include “branching” and “arborization.” Using this analogy, the bark of the tree is analogous to the neuronal cell membrane, the “skin” of the cell. However, unlike the bark of a tree, which is hard and static, the cell membrane is a fatty, flexible boundary that keeps the cell as an entity.
The cell membrane is made up of two layers of fats (called a phospholipid bilayer). Each layer is made up of individual fat molecules shaped like an old-fashioned clothespin. If you imagine a circle made of a double layer of clothespins whose tails face each other, you will have a good mental image of the membrane. The neuronal cell membrane has two primary purposes:
- The cell membrane keeps the inside environment of the cell stable to the appropriate degree. It functions as the gatekeeper, allowing substances to pass in or out of the cell, via specialized pores called ion channels and neurotransmitter pumps. The channels are passageways through which a number of positively and negatively charged elements (e.g., potassium, calcium, sodium, chloride) flow into and out of the cell. Pumps, on the other hand, more actively control the intake or secretion of neurotransmitters into and out of the cell interior.
- The cell membrane also carries electrical signals from one end of the neuron to the other. The difference between the total positive and negative charges inside and outside the cell determines whether a neuron propagates the signal it received on to the next neuron.
Receptors are microscopic, folded, protein structures that are transmembranal (they extend across the cell membrane, from the outside of the cell to the cell interior). When they are combined with the neurotransmitters (called ‘first messengers’ because they are the first in a series of carriers of information or messages from one neuron to the next) that bind to them, a cascade of events (via second and third messengers inside the cell) occurs to convey information from the outside environment of the cell via ion channels, which then close or open, thereby inducing the cell to be stable to a greater (behavioral inhibition) or lesser (behavioral excitation) degree. This immediate cellular response affects the transmission of signals, but does not cause long-term neuronal changes (no learning) to the innermost sanctum of the cell, the nucleus and genes.
Certain receptors initiate long-term changes in the neuron by activating or suppressing certain genes. There are a number of abnormalities of receptor function in medicine, including a type of diabetes in which the receptors do not recognize insulin and a condition called peripheral resistance to thyroid hormone. This latter condition, although rare, is associated with Attention Deficit Disorder.
Receptors have been the focus of a great deal of research in the neurosciences. There are hundreds of different receptor types and subtypes. As more and more receptors are discovered, their nomenclature is becoming more and more complex. Since the newer medications, such as Buspar (buspirone), Risperdal (risperidone), Prozac (fluoxetine), Paxil (paroxetine), Zoloft (sertraline), Effexor (venlafaxine), Wellbutrin (buproprion), and Serzone (nefazodone) are actually targeted to specific receptor classes and subtypes, some familiarity with how they are named will reduce your confusion.
Broadly speaking, receptors are classified into families, such as the dopamine family, serotonin family, and norepinephrine family. The specific subtypes of receptors (new subtypes are discovered almost weekly) are not relevant to your purposes. Receptors are named after the neurotransmitter that binds to it, for example, serotonin receptors. There are only two types of receptors known at this time:
- Gate or ionophore (think “ion-pore”) receptors are made up of four or five transmembranal protein subunits. When one of these receptors is activated, the gates or channels of the cell membrane are immediately opened or closed to the flow of potassium (K +), chloride (CI -), sodium (Na +), calcium (Ca ++), and other charged elements (ions). The net result of this ion flow immediately determines whether the neuron is activated to fire (pass a signal to the next neuron) or inhibited (dormant). These receptors are the site of action of alcohol and the minor tranquilizers, such as Valium.
- G protein linked receptors also span the cell membrane, and are physically linked to an important protein family, the G proteins (over two dozen types have been identified so far). G proteins are the place in the cell where amplification and integration (summation and convergence) of various inputs occur.G proteins are very important in bipolar disorders and may be the site where lithium has its impact. These receptors are made up of seven subunits. Once the neurotransmitter docks in this receptor, the shape of the G protein is altered. This causes a cascade of internal events, which often leads to long-term changes (neuromodulation) in the types and amounts of proteins produced by the neuron and, therefore, long-term changes in its structure and function. The discovery of this receptor type has been critical in understanding how learning and memory occur, as well as the mechanisms involved in addiction.