1. Neurophysiology

Organization  

Neurophysiology  

-Membrane Ion channels  

-Resting membrane potential  

-Membrane potentials as signals  

-Synapses  

-Neurotransmitters & Neuroactive Substances 

Pathophysiology of the nervous system  

Sensory and motor division

Sensory division 

-Sensory afferent fibers carry nerve impulses from skin, skeletal muscle, and joints taking them to the brain.  

-Visceral afferent fibers transmit nerve impulses from your visceral organs to the brain. 

Motor division (no further information) divides into somatic and autonomic NS 

Further divisions of the NS

Somatic nervous system: Conscious control of skeletal muscle contraction 

Autonomic nervous system: It regulates the contractions of smooth muscle cardiac muscle and glands. Divides into sympathetic division and parasympathetic division 

Sympathetic NS: fight or flight response. Mobilizes body systems during activity. 

Parasympathetic division: rest and digest. Conserves energy and promotes house-keeping functions during rest. 

Structure of neurons  body and dendrites

Nerve is collection of numerous neurons 

Body= soma or perikaryon: It contains the nucleus and the nucleolus. It is the major biosynthesis center. The focal point for the outgrowth of neuronal processes. It has well developed ____ bodies. The axon hillock is part of the nerve cell body, the cone shaped region that gives rise to an axon. 

Dendrites: Can be present in a variety of different forms, short or long, they are tapered, and tend to be diffusely branched. These are receptive structures but can also serve as inputs for other neurons. Electrical signals that occur in these structures are conveyed as graded potentials NOT action potentials. 

Structure of neurons axon

Axon: This region is responsible for generating and transmitting action potentials. The axon has terminal regions that vary in their degree of branching, neurotransmitters are released from these axon terminals. Anterograde movement is from the nerve impulse toward the axon terminals. Retrograde movement is from the axon terminals toward the nerve cell body. 

Neurons can shift the type of neurotransmitter they produce, however they will only ever produce one type at a time.

Action potential will remain constant down the entire length of the axon. Always the same despite what neurotransmitter 

Plasma Membrane  

• Bimolecular layer of lipids and proteins in a constantly changing fluid mosaic  

• The plasma membrane is a selective barrier that allows sufficient passage of oxygen, nutrients, and waste to service the volume of every cell  

• Integral proteins  

-Functions: Transport proteins (channels & carriers), enzymes or receptors  

• Peripheral proteins  

-Functions: Enzymes, motor proteins, cell-to-cell links, provide support on intracellular surface. 

MEMBRANE TRANSPORT MECHANISMS  

Passive Processes (ATP is not required) 

A) Simple diffusion of fat-soluble molecules directly through the phospholipid bilayer (non polar or lipid substances) 

B) Carrier-mediated facilitated diffusion via protein carrier specific for one chemical; binding of substrate causes transport protein to change shape 

Channel-mediated facilitated diffusion Osmosis

C) Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge 

Moves substances across the plasma membrane by two possible ways 1. leakage channels: always open  2. gated channels: 3 ways they can be opened and we will talk more about them soon 

For B and C (facilitated) allows for the passage of lipid insoluble substances

D) Osmosis, diffusion of a solvent such as water through a specific channel protein (aquaporin) or through the lipid bilayer 

Integral proteins: Membrane Ion channels  

Types of ion channels:  

• Chemically-gated (aka ligand-gated): stimulated by chemicals (ie. Neurotransmitters)  Open in response to binding of appropriate neurotransmitter 

 • Voltage-gated: respond to changes in membrane potential 

• Mechanically gated: respond to physical changes in the shape of the receptor by touch or pressure  

Still all passive processes don't use ATP 

Active Processes (ATP is utilized) 

1. Primary active transport- The ATP driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell 

2. Secondary active transport-As Na+ diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell 

Sodium potassium pumps are in every cell in your body 

Active processes less concentrated to more concentrated (up the gradient) requires energy. 

The ATP powered pump requires that ATP be hydrolyzed to remove one of the terminal inorganic phosphates. That free inorganic phosphate is used to phosphorylate the transport protein allowing it to change shape and thus function as a pump. 

Primary and secondary transport more details

Primary active transport is a direct transport. 

Secondary active transport- the ATP powered pump indirectly drives the process as charged substances are transported across the membrane against their concentration gradient, the pump stores the energy in the ionic gradient that they create. As some of the charged substances leak back across the plasma membrane it drives the transport of other substances in the process. 

Vesicular transport and phagocytosis

Vesicular transport- This involves the movement of fluids containing particles that are too large to pass through channels and pumps. They must be packaged inside a membranous sac (the vesicle) to be moved in (endocytosis), or out (exocytosis), or across (transcytosis).  Large or solid materials

A) Phagocytosis- The cell engulfs a large particle by forming projecting pseudopods around it and enclosing it within a membrane sac called a phagosome. The phagosome is combined with a lysosome. Undigested contents remain in the vesicle or are ejected by exocytosis. Vesicle may or may not be protein coated but has receptors capable of binding to microorganisms or solid particles 

Pinocytosis and receptor mediated endocytosis

B) Pinocytosis- The cell gulps a drop of extracellular fluid containing solutes into tiny vesicles. No receptors are used, so the process is nonspecific. Most vesicles are protein-coated.  

Small volumes of liquid with dissolved materials are brought into the cell. They encounter protein coated pits which then triggers the membrane to fold around the material, typically the substance is clathrin. 

C)Receptor-mediated endocytosis- Extracellular substances bind to specific receptor proteins, enabling the cell to ingest and concentrate specific substances (ligands) in protein-coated vesicles. Ligands may simply be released inside the cell, or combined with a lysosome to digest contents. Receptors are recycled to the plasma membrane in vesicles.   

There are receptors for specific substances present on the plasma membrane. Once these substances bind their specific receptors they will be taken inside of the cell inside this protein coated vesicle 

PLASMA MEMBRANE: Generating a Resting Membrane Potential 

1. K+ diffuse down their steep concentration gradient out of the cell via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face. 

   2.K+ also move into the cell because they are attracted to the negative charge established on the inner plasma membrane face. 

   3. A negative membrane potential (-90mV) is established when the movement of K+ out of the cell equals K+ movement into the cell. At this point, the concentration gradient promoting K+ exit exactly opposes the electrical gradient for K+ entry. 

PLASMA MEMBRANE: Generating a Resting Membrane Potential  potassium ion and concentrations

The resting membrane potential is mainly determined by potassium ions, specifically the potassium gradient and the differential permeability of the membrane to potassium compared to other ions. Potassium ions are 10X more concentrated inside the cell, in an unstimulated cell K+ will leave the cell through leakage channels. There is a higher number of K+ leakage channels compared to that of other ions, thus your cells are more permeable to potassium. 

PLASMA MEMBRANE: Generating a Resting Membrane Potential  EXTRA Details pt2

The loss of potassium ions makes the inside of the plasma membrane more negative. In nerve cells, this will reach a limit of –90mV at this point potassium channels will allow for a K+ ion to be brought into the cell for each K+ ion allowed out of the cell (these channels are voltage gated). Maintaining a resting membrane potential is key, you have to pump in 2K+ and out 3Na+, sodium is pumped out because water follows sodium. 

Resting Membrane Potential 

 •The potential difference (–70 mV) across the membrane of a resting neuron 

 •It is generated by different concentrations of Na+, K+, Cl− & protein anions (A−)  

•Ionic differences are the consequence of:  

✓Cell membrane’s differential permeability to Na+ & K+  (allows change) 

✓Operation of the Na+/K+ pump  (maintains stable) 

Na+ conc exterior 150mM. Na+ conc interior is 15mM. 

K+ conc exterior 5mM. K+ conc interior is 150mM. 

Measuring Membrane Potential 

Voltage: measure of potential energy generated by areas of separated charge. Measured in V or mV. 

Potential difference: Voltage measured between two points 

Current: flow of electrical charge between the two points. Measured in Amps (A) 

Resistance: The hindrance to the flow or charge (current) 

Insulator: Substance with high electrical resistance 

Conductor: Substance with low electrical resistance 

Membrane potential changes

 Membrane potential changes are produced by: 1. Changes in membrane permeability to ions. 2. Alteration of ion concentrations across the membrane. 

2 types of membrane potentials: 1. Graded potentials 2. Action potentials 

Action Potentials (APs)  

• An action potential in the axon of a neuron = a nerve impulse  

• A brief reversal of membrane potential  

• Total amplitude of voltage change = 100 mV  

• Only generated by muscle cells & neurons  

• Does not decrease in strength over distance  

• The principal means of neural communication 

Where does most action potential in neurons originate

Most action potential in neurons originate near the axon hillock. Propagation of an action potential occurs as the voltage charge spreads along the plasma membrane due to the opening of voltage gated sodium channels along the plasma membrane. The change in membrane voltage is from –70mV to +30mV ( a total change of 100mV typically) 

1. Resting State 

 • Na+ and K+ channels are closed Leakage accounts for small amount of Na+ & K+ movement  

• Each Na+ channel has 2 voltage-regulated gates: 

 ✓Activation gates: closed in the resting state  

✓Inactivation gates: open in the resting state  

2. Depolarization Phase  

• Na+ permeability increases; membrane potential reverses  

• Na+ gates are opened; K+ gates are closed 

Leakage accounts for a small amount of K+ movement  

• Threshold = a critical level of depolarization (-55 to -50 mV)  

• At threshold, depolarization becomes self-generating  

Activation gates are open. Na+ channels are open. Inactivation gates??   

3. Repolarization Phase  

• Na+ inactivation gates close  

• Membrane permeability to Na+ declines to resting levels  

Leakage accounts for small amount of Na+ movement  

• As sodium gates close, voltage-sensitive K+ gates open  

• K+ exits the cell & the internal negativity of the resting neuron is restored  

4. Hyperpolarization 

 • Na+ activation gates are closed (resting position)  

• Na+ inactivation gates are open (resting position) 

 Leakage accounts for small amount of Na+ movement  

• K+ gates remain open, causing an excessive efflux of K+  (outward movement) 

• This efflux causes hyperpolarization of the membrane (undershoot)  

• The neuron is insensitive to stimulus & depolarization during this time (gives time to repair and recoup) 

Know state of gates and permeability