Neurophysiology

Transmission of an action potential. This occurs in two ways:

1) across the synapse - synaptic transmission. This is a chemical process, the result of a chemical neurotransmitter.

2) along the axon - membrane transmission. This is the propagation of the action potential itself along the membrane of the axon.

Synaptic transmission - What you learned about the neuromuscular junction is mostly applicable here as well. The major differences in our current discussion are:

1) Transmission across the synapse does not necessarily result in an action potential. Instead, small local potentials are produced which must add together in summation to produce an action potential.

2) Although ACh is a common neurotransmitter, there are many others and the exact effect at the synapse depends on the neurotransmitter involved.

3) Neurotransmitters can be excitatory or inhibitory. The result might be to turn off the next neuron rather than to produce an action potential

The basic steps of synaptic transmission are the same as described at the neuromuscular junction

1) Impulse arrives at the axon terminus causing opening of Ca²⁺ channels and allows Ca²⁺  to enter the axon. The calcium ions are in the extracellular fluid, pumped there much like sodium is pumped. Calcium is just an intermediate in both neuromuscular and synaptic transmission.

2) Ca²⁺  causes vesicles containing neurotransmitter to release the chemical into the synapse by exocytosis across the pre-synaptic membrane.

3) The neurotransmitter binds to the post-synaptic receptors. These receptors are linked to chemically gated ion channels and these channels may open or close as a result of binding to the receptors to cause a graded potential which can be either depolarization, or hyperpolarization depending on the transmitter. Depolarization results from opening of Na⁺ gates and is called an EPSP. Hyperpolarization could result from opening of K⁺ gates and is called IPSP. 

4) Graded potentials spread and overlap and can summate to produce a threshold depolarization and an action potential when they stimulate voltage gated ion channels in the neuron's trigger region.

5) The neurotransmitter is broken down or removed from the synapse in order for the receptors to receive the next stimulus. As we learned there are enzymes for some neurotransmitters such as the Ach-E which breaks down acetylcholine. Monoamine oxidase (MAO) is an enzyme which breaks down the catecholamines (epinephrine, nor-epinephrine, dopamine) and nor-epinephrine (which is an important autonomic neurotransmitter) is removed by the axon as well in a process known as reuptake. Other transmitters may just diffuse away.

Graded Potentials - these are small, local depolarizations or hyperpolarizations which can spread and summate to produce a threshold depolarization. Small because they are less than that needed for threshold in the case of the depolarizing variety. Local means they only spread a few mm on the membrane and decline in intensity with increased distance from the point of the stimulus. The depolarizations are called EPSPs, excitatory post-synaptic potentials, because they tend to lead to an action potential which excites or turns the post-synaptic neuron on. Hyperpolarizations are called IPSPs, inhibitory post-synaptic potentials, because they tend to inhibit an action potential and thus turn the neuron off.

Summation - the EPSPs and IPSPs will add together to produce a net depolarization (or hyperpolarization).

Temporal summation- this is analogous to the frequency (wave, tetany) summation discussed for muscle. Many EPSPs occurring in a short period of time (e.g. with high frequency) can summate to produce threshold depolarization. This occurs when high intensity stimulus results in a high frequency of EPSPs.

Spatial summation - this is analogous to quantal summation in a muscle. It means that there are many stimuli occurring simultaneously. Their depolarizations spread and overlap and can build on one another to sum and produce threshold depolarization.

Inhibition - When the brain causes an IPSP in advance of a reflex pathway being stimulated, it reduces the likelihood of the reflex occurring by increasing the depolarization required. The pathway can still work, but only with more than the usual number or degree of stimulation. We inhibit reflexes when allowing ourselves to be given an injection or blood test for instance.

Facilitation - When the brain causes an EPSP in advance of a reflex pathway being stimulated, it makes the reflex more likely to occur, requiring less additional stimulation. When we anticipate a stimulus we often facilitate the reflex.

Learned Reflexes - Many athletic and other routine activities involve learned reflexes. These are reflex pathways facilitated by the brain. We learn the pathways by performing them over and over again and they become facilitated. This is how we can perfect our athletic performance, but only if we learn and practice them correctly. It is difficult to "unlearn" improper techniques once they are established reflexes. Like "riding a bike" they may stay with you for your entire life!

Post-tetanic potentiation - This occurs when we perform a rote task or other repetitive action. At first we may be clumsy at it, but after continuous use (post-tetanic) we become more efficient at it (potentiation). These actions may eventually become learned reflexes

The Action Potential

The trigger region of a neuron is the region where the voltage gated channels begin. When summation results in threshold depolarization in the trigger region of a neuron, an action potential is produced. There are both sodium and potassium channels. Each sodium channel has an activation gate and an inactivation gate, while potassium channels have only one gate. 

A) At the resting state the sodium activation gates are closed, sodium inactivation gates are open, and potassium gates are closed. Resting membrane potential is at around -70 mv inside the cell. 

B) Depolarizing phase: The action potential begins with the activation gates of the sodium channels opening, allowing Na+ ions to enter the cell and causing a sudden depolarization which leads to the spike of the action potential. Excess Na+ ions enter the cell causing reversal of potential becoming briefly more positive on the inside of the cell membrane.

C) Repolarizing phase: The sodium inactivation gates close and potassium gates open. This causes Na+ ions to stop entering the cell and  K+ ions  to leave the cell, causing repolarization. Until the membrane is repolarized it cannot be stimulated, called the absolute refractory period.

D) Excess potassium leaves the cell causing a brief hyperpolarization. Sodium activation gates close and potassium gates begin closing. The sodium-potassium pump begins to re-establish the resting membrane potential. During hyperpolarization the membrane can be stimulated but only with a greater than normal depolarization, the relative refractory period.

Action potentials are self-propagated, and once started the action potential progresses along the axon membrane. It is all-or-none, that is there are not different degrees of action potentials. You either have one or you don't.

Cells, cytoplasm, and organelles:

• Cytoplasm consists of a gelatinous solution and contains microtubules (which serve as a cell's cytoskeleton) and organelles

• Cells also contain a nucleus within which is found DNA (deoxyribonucleic acid) in the form of chromosomes plus nucleoli (within which ribosomes are formed)

• Organelles include:

1. Endoplasmic reticulum : 2 forms: smooth and rough; the surface of rough ER is coated with ribosomes; the surface of smooth ER is not , Functions include: mechanical support, synthesis (especially proteins by rough ER), and transport
2. Golgi complex consists of a series of flattened sacs (or cisternae) functions include: synthesis (of substances likes phospholipids), packaging of materials for transport (in vesicles), and production of lysosomes
3. Lysosome : membrane-enclosed spheres that contain powerful digestive enzymes , functions include destruction of damaged cells & digestion of phagocytosed materials
4.  Mitochondria : have double-membrane: outer membrane & highly convoluted inner membrane
   1. inner membrane has folds or shelf-like structures called cristae that contain elementary particles; these particles contain enzymes important in ATP production
   2. primary function is production of adenosine triphosphate (ATP)
5. Ribosome-:composed of rRNA (ribosomal RNA) & protein , primary function is to produce proteins
6. Centrioles :paired cylindrical structures located near the nucleas , play an important role in cell division
7. Flagella & cilia - hair-like projections from some human cells
   1. cilia are relatively short & numerous (e.g., those lining trachea)
   2. a flagellum is relatively long and there's typically just one (e.g., sperm)

• • Villi  Projections of cell membrane that serve to increase surface area of a cell (which is important, for example, for cells that line the intestine)

Lipids:

• about 40% of the dry mass of a typical cell
• composed largely of carbon & hydrogen
• generally insoluble in water
• involved mainly with long-term energy storage; other functions are as structural components (as in the case of phospholipids that are the major building block in cell membranes) and as "messengers" (hormones) that play roles in communications within and between cells
• Subclasses include:
  • Triglycerides - consist of one glycerol molecule + 3 fatty acids (e.g., stearic acid in the diagram below). Fatty acids typically consist of chains of 16 or 18 carbons (plus lots of hydrogens).
  • phospholipids - Composed of 2 fatty acids, glycerol, phosphate and polar groups , phosphate group (-PO⁴) substitutes for one fatty acid & these lipids are an important component of cell membranes

steroids - have 4 rings- cholesterol, some hormones, found in membranes include testosterone, estrogen, & cholesterol

Blood is a liquid tissue. Suspended in the watery plasma are seven types of cells and cell fragments.

• red blood cells (RBCs) or erythrocytes
• platelets or thrombocytes
• five kinds of white blood cells (WBCs) or leukocytes
  • Three kinds of granulocytes
    • neutrophils
    • eosinophils
    • basophils
  • Two kinds of leukocytes without granules in their cytoplasm
    • lymphocytes
    • monocytes

Normal Chemical Composition of Urine

Urine is an aqueous solution of greater than 95% water, with a minimum of these remaining constituents, in order of decreasing concentration:

Urea 9.3 g/L.

Chloride 1.87 g/L.

Sodium 1.17 g/L.

Potassium 0.750 g/L.

Creatinine 0.670 g/L .

Other dissolved ions, inorganic and organic compounds (proteins, hormones, metabolites).

Urine is sterile until it reaches the urethra, where epithelial cells lining the urethra are colonized by facultatively anaerobic gram-negative rods and cocci. Urea is essentially a processed form of ammonia that is non-toxic to mammals, unlike ammonia, which can be highly toxic. It is processed from ammonia and carbon dioxide in the liver.