Systems Physiology - Human Anatomy and Physiology

When at rest, the neuron initially has a negative membrane potential. At the beginning of an action potential, voltage-gated sodium channels open, allowing sodium ions to enter the cell. This causes the cell to become positively charged compared to the outside of the cell. This process is called depolarization.

After depolarization occurs, the sodium channels close, initiating the absolute refractory period. Voltage-gated potassium channels then open and potassium ions exit the cell. This results in hyperpolarization and the relative refractory period. The potassium channels then close and the sodium-potassium pump returns the cell to its resting potential by removing sodium and collecting potassium.

Once an action potential has been created, the membrane has a period of time during which it cannot be stimulated to create another action potential. The absolute refractory period occurs when the voltage-gated sodium channels initially close. The first gating mechanism of these channels cannot be overcome by an electrical stimulus, and the sodium channels will remain closed even if a large electrical stimulus is present. During this period, even a very large stimulus cannot result in neural depolarization.

Following this, the secondary gating mechanism for the channel becomes active. This mechanism is sensitive to electrical stimuli, but keeps the channels closed when the neuron is at rest. The relative refractory period results when sodium channels are capable of opening, but the cell is hyperpolarized, making it very difficult to initiate a stimulus that reaches the action potential threshold.

The neuron has a resting potential. In its resting state, the neuron has a resting potential with a slightly negative interior compared to the exterior. Sodium ions enter the cell and alter the membrane potential. Through voltage-gated channels, enters and makes the interior less negative therefore decreasing the membrane potential difference, which is known as depolarization. The membrane potential depolarizes all the way up to the threshold level. After enough enters, the threshold membrane potential is reached. This opens more channels. An action potential is fired, which means that the depolarization spreads down the neuron's axon. This travels down the entire axon, eventually reaching the dendrite and signaling to other neurons.

The voltage-gated channels along the axonal plasma membrane open and close in response to changes in voltage, and may exist in three distinct states: deactivated, activated, and inactivated. While the axon is at rest, these channels are said to be deactivated; they are impermeable to sodium ions since their activation gates are closed. Once the neuron gets depolarized to the threshold of the voltage-gated sodium channels, the activation gates open, allowing the influx of sodium down its concentration gradient into the cell. During this time the channels are in their activated state. At the peak of the action potential the activation gates are still open, but the inactivation gates close, stopping the flow of sodium through the channels. The channels are in the inactivated state due to the cell becoming depolarized. Once the membrane potential drops back down towards resting, the inactivation gates open, and the activation gates close, thereby deactivating the channels again, until another action potential depolarizes the membrane.

To support the general function of the nervous system, neurons must communicate within the cell (intracellular signaling) and between other cells (intercellular signaling). In order to achieve long distance and rapid communication, neurons have special abilities for sending electrical signals (action potentials) along axons. This mechanism is called conduction, and it is how the neuron's cell body communicates with its own terminals via the axon. Communication between neurons is achieved at synapses by the process of neurotransmission.

At resting potential, the cell membrane is about 25 times more permeable to potassium ions than it is to sodium ions. During an action potential, the membrane becomes much more permeable to sodium ions than potassium ions, causing the membrane potential to become more positive, as sodium flows down its concentration gradient into the cell. Note that this concentration gradient is largely set up by the action of the sodium-potassium ATPase, which pumps three sodium ions out of the cell in exchange for two potassium ions into the cell.

A synapse is a specialized junction between cells. It is involved in the integration and converging of signals between neurons. At a synaptic junction, the membranes of the pre- and post- synaptic neurons are separated by a gap called a synaptic cleft, which is the site of neurotransmitter release.

Glutamate opens sodium channels in the plasma membrane of the receiving neuron, moving the action potential towards (depolarize) the sodium Nernst potential (81mV). GABA is an inhibitory neurotransmitter which opens chloride channels in the plasma membrane of the receiving neuron, making the neuron more difficult to excite (hyperpolarized).

The action potential of a neuron is generate at the axon hillock and is propagated down the axon and to the terminal branches where it will synapse with the dendrites of the next neuron.

Depolarization is when the neuron becomes more positive by gaining positively charged ions, specifically sodium ions. During depolarization the sodium ion channels open and sodium ions enter the neuron, reducing the membrane potential to roughly +35 mV.

In order to have an action potential, you must have a depolarization. Na channels must close before K channels open

Myelin helps to increase resistance along the axon, which helps to propagate the action potential along the axon.

The influx of positive sodium ions into the neuron is known as depolarization. This is the loss of negative charge that occurs when positive sodium passes through the neural membrane and enters the neuron.

The resting membrane potential is based on the difference in electrical charges of the ions that flow through the membrane. The membrane potential has a greater permeability to potassium when at rest which causes a shift in its potential. Thus, potassium has the strongest affect on the RMP and causes it to be closer to potassium's reversal potential. Side note: This potential is strongly held by the sodium potassium pump.

If an already positive membrane potential becomes more positive, it is becoming hyperpolarized because the electrical difference between the inside and outside of the cell is getting larger. On the other hand, a stimulus that moves the potential difference closer to 0 is depolarizing because it is decreasing the difference in electrical potential between the inside and outside of the cell.

Bone growth has multiple steps that allow growth in both length and width. One thing to remember is the functions of the bone cells during growth and development. Osteoclasts are responsible for "hollowing out" the center of long bones, which makes for larger cavities within the diaphysis. Osteoblasts, on the other hand, are responsible for laying down additional bone matrix on the outsides of the bones.

As bone cells mature, they become further embedded within subsequent layers of the bony matrix. Osteogenic cells, which give rise to osteoblasts, are located in the outer periosteum of the bone. When damage occurs to the bone, osteogenic cells differentiate and begin repairing the bony matrix from the outside.

Bone is a dynamic tissue that remodels under mechanical stress, or orthodonture. Mechanical stress in bone generates electric potential via the piezoelectric effect. Negative potential results in bone deposition (bone is laid down) whereas positive potential results in bone resorption (bone is broken down).

Histologically, the epiphyseal growth plate is divided into five zones. From epiphysis to diaphysis they are the resting zone, zone of proliferation, zone of maturation, zone of calcification, and zone of ossification. At the growth plate, cartilage is constantly being developed into the bone of the diaphysis. The stages of this process align with the regions of the epiphyseal plate. The resting zone houses quiescent chondrocytes that are not yet active in bone synthesis. The zone proliferation is characterized by chondrocyte mitosis and replication. These cells then develop and grow with in the zone of maturation. Eventually the cells reach their maximum growth and undergo apoptosis to release cell contents in the zone of calcification. This prevents cartilage from infiltrating the bony region of the diaphysis. The chondrin matrix begins to calcify in this zone as well. As calcification progresses and the organic cartilage matrix is replaced by bony hydroxyapatite mineral in the zone of ossification, the epiphyseal plate completely replaces the original chondrocytes with bone.

As more bone is produced, the epiphyseal plate is pushed farther and farther away from the midpoint of the bone. The lengthening of the bone ends when the zones of the epiphyseal plate fuse and further growth becomes impossible.

There are three primary types of bone cell: osteoblasts, osteocytes, and osteoclasts. Osteoblasts are responsible for creating new bone by sequestering minerals and generating new hydroxyapatite matrix. Osteoclasts break down this matrix, releasing the minerals into the blood. Osteocytes are mature osteoblasts that have become embedded in the matrix of the bone and serve primarily for communication purposes.

Satellite cells are located at the periphery of muscle cells and are capable of dividing and giving rise to new myoblasts. Satellite cells are, essentially, adult muscle stem cells. Common lymphoid progenitor cells are another type of adult stem cell, housed in red bone marrow, and are responsible for regenerating the erythrocyte population of the body, as well as producing lymphocytes.