The concentration of chloride is low inside the cell compared to the outside. Although the tendency exists for diffusion to dissipate this concentration gradient, chloride ions feel a repulsive force from the negative membrane potential inside the cell. Chloride flux tends to occur mostly when the cell is depolarized by an excitatory event. Chloride currents are usually inhibitory.
Calcium: This ion is found in very low (nanomolar to micromolar) concentrations inside neurons because it is heavily buffered by calcium chelating (binding) molecules. Calcium can enter cells through calcium-specific channels and some neurotransmitter channels such as NMDA glutamate receptors and alpha-7 nicotinic acetylcholine receptors. Calcium modulates second messenger cascades inside cells that regulate ion channels from the inside, and may also affect gene expression. The flux of calcium through voltage-dependent calcium channels results in the release of neurotransmitters from axon (the part of the neuron that conducts impulses away from the cell) terminals.
Magnesium: Normally magnesium does not pass through neuronal membranes. However, when the neuron is close to the resting potential, magnesium, attracted to the negative charge inside, binds in the extracellular “mouth” of the NMDA glutamate receptor. This receptor will not open unless, in addition to binding glutamate released from a pre-synaptic axon terminal, the membrane is partially depolarized. This depolarization (which is often provided by nearby non-NMDA excitatory receptors) reduces the potential across the membrane and thereby favors the release of the magnesium ion, allowing sodium and some calcium to flow through the channel.
Sizing up proteins
Membrane ion channels and receptors are typically composed of several proteins called subunits that, when assembled in the membrane, form a receptor or ion channel. At least 1,000 different receptor types exist in the olfactory (smell) system alone, each with a different combination of protein subunits with varying structures. The majority of ion channels and receptors have from four to six protein subunits.
Going through membrane proteins
Membrane proteins have a three-dimensional configuration. One end of the protein is either in the intracellular or extracellular fluid, the transmembrane region resides within the phospholipid membrane, and the protein terminal, like the beginning, is either in the intracellular or extracellular fluid. Most membrane protein subunits make multiple loops that are embedded in the membrane.
Peeking at the Parts of a Cell
Neurons are cells. Like all eukaryotic cells they have a nucleus with chromosomes made of DNA, surrounded by a nuclear membrane. Outside this nuclear membrane is the cytoplasm, which is surrounded by the cell membrane. The following sections discuss the parts of the neuronal cell that are common with other eukaryotic cells, and later sections discuss the differences.
Cytoplasm and organelles
Within the neuronal cytoplasm are typical eukaryotic organelles (or, plainly, parts of the cell). The following organelles reside in the cytoplasm:
Mitochondria: These are self-replicating organelles that generate adenosine triphosphate (ATP), the cell’s main energy source. ATP is generated by a process called oxidative phosphorylation, in which energy from electron transfer involving oxygen adds a phosphate to adenosine diphosphate (ADP). Mitochondria have their own DNA and multiply by cell division on their own, as needed for the cell’s energy requirements. Neurons have very high concentrations of mitochondria compared to other cells.
Endoplasmic reticulum (ER): The ER is an organelle composed of flattened tubes (cisternae) involved in protein synthesis, and carbohydrate and lipid metabolism, among other functions. ER has two forms: rough and smooth. Rough ER contains ribosomes where mRNA is used to synthesize proteins from amino acids. Smooth ER synthesizes steroids, phospholipids, and other lipids. One of its functions in neurons is the modification of cell membrane proteins that will become receptors. It also regulates (sequesters) calcium ion concentration.
Golgi apparatus: This organelle processes proteins and lipids that are synthesized by the cell. This is also where peptide neurotransmitters may be packaged into vesicles that are suitable to release outside the cell.
Lysosomes and peroxisomes: These two organelles use enzymes to digest viruses or bacteria that have entered the cell, and non-functioning organelles. Peroxisomes use enzymes to degrade toxic peroxides.
Centrosome: The centrosome is a cytoskeletal organizer. It consists of two centrioles (cylinder-shaped cell structures) that separate during cell division to form the mitotic spindle. Centrosomes are organizing centers for microtubules, which make up a large portion of the overall cytoskeleton. Microtubules are particularly important in extended neural processes such as dendrites and axons. The centrosome also controls transport of proteins through the Golgi apparatus and ER.
Nucleus
The nucleus contains the cell’s chromosomes and is where DNA replication and RNA transcription occur. The nucleus has a double membrane called the nuclear envelope that separates it from the cytoplasm. Many neurons have a prominent nucleolus, a small region within the nucleus where ribosome subunits are assembled. There are pores in the nuclear membrane through which mRNA passes to the cytoplasm after being synthesized in the nucleus.
Secretion and hormones
Cellular secretion is the process of releasing substances that cause changes in other cells, usually, or even the secreting cell. Secretion may have evolved from excretion (the release of waste products). Although many secretion mechanisms exist, secretion typically involves vesicles transiently docking and fusing with the cell membrane, thereby releasing their contents into the extracellular space. Some secretion occurs from porosomes, which are permanent secretory structures at the cell plasma membrane.
Secreted signals are often hormones — chemicals released by a cell in one part of the organism that act as messages to cells in other parts of the organism. Hormones may travel in the extracellular space (which is called paracrine signaling) or be transported in the blood. Target cells that express a specific hormone receptor can respond when that hormone binds the receptor. This activates a cascade of signals, producing hormone-induced responses. Mechanisms exist to degrade the hormone so the cycle can begin again.
Proteins that are to be secreted are synthesized by ribosomes located on the rough ER. Sugar molecules are then added in a process called glycosylation, and the protein begins to fold with the help of special proteins called molecular chaperones. Vesicles containing the secretory proteins bud from the ER membrane and travel to the Golgi apparatus. In the Golgi apparatus, where further post-translational modifications may occur, the proteins are encapsulated in secretory vesicles. These vesicles are transported via the cytoskeleton to their destination at the plasma membrane. (Sometimes post-translational modifications occur within the vesicles.) Finally, the vesicle contents are released outside the cell (the process is called exocytosis) when the vesicle fuses with the cell membrane.
