Systems of Pharmacology II: Exam 1

What are the functions of the nervous system?

• collect information

• process information

• elicit response to information

What is sensory input to the central nervous system?

afferent

What is motor output to the central nervous system?

efferent

What are the characteristics of the central nervous system (CNS)?

• brain and spinal cord

• integrative and control centers

What are the characteristics of the peripheral nervous system?

• cranial nerves and spinal cord

• communication lines between the CNS and the rest of the body

What are the characteristics of the sensory (afferent) division?

• somatic and visceral sensory nerve fibers

• conducts impulses from receptors to the CNS

What are the characteristics of the motor (efferent) division?

• motor nerve fibers

• conducts impulses from the CNS to effectors (muscles and glands)

What are the characteristics for the somatic nervous system?

• somatic motor (voluntary)

• conducts impulses from the CNS to skeletal muscles

What are the characteristics of the autonomic nervous system (ANS)?

• visceral motor (involuntary)

• conducts impulses fro the CNS to cardiac muscles, smooth muscles, and glands

What are characteristics of the sympathetic division?

• mobilizes body systems during activity

• correlates with stress (fight or flight response)

What are the characteristics of parasympathetic division?

• conserves energy

• promotes house-keeping functions during rest

• correlates with peace

What is the autonomic motor communication between PNS and CNS?

• ventral: body cavity (heart, lungs, arterioles, bladder, pancreas, GI tract)

• and eye, salivary and sweat glands

What is the somatic motor communication between PNS and CNS?

• limbs and body wall

What is the sensory communication between PNS and CNS?

• dorsal (body cavity)

What are the characteristics of neurons?

• conduct electrical impulses

  • sensory = detect stimuli

  • motor = transmit signals from CNS

• interneurons

  • process signals between neurons

  • most abundant type of neuron

What is the job of glial cells (“glue” cells)?

support neurons

What type of glial cells are there?

• astrocytes (*most important)

• microglia (immune cells of CNS)

• ependymal cells (secrete and circulate CFS)

• oligodendrocytes and schwann cells (myelinating)

• satellite cells in PNS (don’t need to worry about)

What are the characteristics of the astrocytes?

• most abundant glial cells

• anchor neurons to capillaries

• guide migration of neurons and synapse formation

• “mop up” leaded ions and neurotransmitters

• some release neurotransmitters

Why are astrocytes important?

they make sure neurons are not too irritable (makes one overreact)

What are the characteristics of microglia?

• monitor health of neurons

• migrate towards injured neurons

• transform into macrophages and engulf and digest dead neurons and invading microorganisms

• important to have these because all other immune cells cannot cross BBB

What are the characteristics of ependymal cells?

• line cavities of brain (ventricles) and spinal cord (canal)

• barrier between nervous tissue and cerebrospinal fluid (CSF)

• ciliated

• secrete CSF, circulate CSF, and cushion the brain and the spinal cord

What are the characteristics of Oligodendrocytes and Schwann cells?

• CNS - oligodendrocytes

  • branched

  • wrap around neurons to form myelin sheath

• PNS - Schwann cells

  • surround larger nerve fibers and form myelin sheath

What is the white matter in Schwann cells and axons in PNS?

myelinated areas

What is the gray matter in Schwann cells and axons in PNS?

unmyelinated areas

What is an unmyelinated axon?

Schwann cells that only wrap around groups of axons once

What is true about the divisions of the nervous system?

the sympathetic nervous system is part of the autonomic nervous system

White matter is only found in the CNS?

false

Which of the following is correctly matched with their functions?

Schwann cells - myelinate neurons in PNS

What is the axon hillock?

where action potentials are generated

What is important to note about neuronal anatomy?

• groups of cell bodies are nuclei in the CNS and ganglia in the PNS

• bundles of axons are tracts in CNS and nerves in PNS

• axons depends on soma for proteins

The myelin sheath does not contain protein

false

What is the role of the dendrites?

input of information and integration

What is the role of the soma?

(cell body or perikaryon) cellular maintenance and information processing

What is the role of the axon?

information transport

What is the role of nerve terminals?

output of information

What is important neuronal characteristics?

• extreme longevity - last an entire lifetime

• amitotic - can not divide

  • in most cases, cannot be replaced if destroyed

• high metabolic rate - need a lot of glucose and oxygen

  • 20% of our body’s energy goes to the brain

  • PET scans and fMRI measures this

What are multipolar neurons?

motor and interneurons

What are bipolar neurons?

sensory neurons, axon that goes in a single direction

What are unipolar neurons?

sensory neurons, axon that goes in two directions

What is the role of terminal branches?

make synapses on target cells

What is the role of multipolar neurons?

receptive region (receives stimulus). Plasma membrane exhibits chemically gated ion channels

What is the role of the bipolar neurons?

conducting region (generates/transmits action potential). Plasma membrane exhibits voltage-gated Na+ and K+ channels

What is the role of unipolar (Pseudounipolar) neurons?

secretory region (axon terminals release neurotransmitters). Plasma membrane exhibits voltage-gated Ca+ channels

What does it mean when separated charges have opposite signs?

there is potential energy

What is Voltage (V)?

unit of measure of that potential energy of separated charge

How is voltage measured?

Always measured as the difference of the inside wrt outside of cell (potential)

What is a current (I)?

flow of electrical charge

What is Resistance (R)?

hindrance to charge flow

What is Ohm’s law?

-I = V/R or V = IR

In a cell, what causes resistance?

the plasma membrane

Why is there so little intracellular Cl-?

Has loss of negative charged macromolecules

Why do ions move?

for concentration and to balance charge

An increase in potential will do what to the current?

increase

When Na+ channels open, what goes in and what comes out?

sodium goes in and potassium goes out

The movement of NGF through the axon is through ___ transport

retrograde

When potassium channels open, potassium current will travel ___ the cell

out of

Which channel is expressed in the secretory region of the neuron?

voltage-gated calcium channels

If the interior of the cell becomes more negative, the rate of K+ flow out of the cell will not change.

false

What is equilibrium membrane potential?

the point for an ion where the electric field counteracts the force due to diffusion. Determined by the Nernst equation

What is the comparison of cytosol compared to the extracellular fluid for equal membrane potential?

the cytosol has a much higher concentration of potassium ions (K+) and impermeable anions (M-) relative to the extracellular fluid

How is membrane potential created?

As K+ ions diffuse out of the cell (from left to right), the impermeable anions are left behind, creating a membrane potential. The magnitude of the membrane potential increases until an equilibrium is reached.

What are the characteristics of K+ in equilibrium membrane (Veq) potentials?

• -91.0 mV

• the voltage where the chemical force that “pushes” K+ OUT of the cell is EQUAL to the electrical force that keeps K+ IN the cell

What are the characteristics of Na+ in equilibrium membrane (Veq) potentials?

• 61.5 mV

• the voltage where the chemical force that “pushes” Na+ INTO the cell is EQUAL to the electrical force that keeps Na+ OUT of the cell

How are intraneuronal and extraneuronal ion concentration maintained?

1. Na+/K+ ATPase/pump (2 K+ in, 3 Na+ out)

2. flow through ion selective channels

• constitutively active (non-gated_

  • leak channels

  • more K+ than Na+ leak (100X)-membrane is more permeable to K+

  • voltage gated

  • ligand gated

  • mechanically gated

What are representative example of voltage-gated cation channels?

• voltage-gated Na+ channels

• voltage-gated K+ channels (including delayed and early)

• voltage-gated Ca2+ channels

What are representative examples of transmitter-gated ion channels?

• acetylcholine-gated cation channels

• glutamate-gated Ca2+ channels

• serotinin-gated cation channels

• GABA-gated Cl- channels

• glycine-gated Cl- channels

Which of the gated channels are insensitive to changes in voltage?

transmitter-gated ion channels

What are the characteristics of voltage-gated sodium channels?

• changes in voltage will increase the likelihood that the channel will be open

• take a long time to get out of the inactive state

What are transitions between resting, activated, and inactivated states dependent on?

membrane potential and time

What are the types of potentials?

• resting membrane

• graded-travels a short distance

• action-travels a long distance

How is voltage measured?

• always measured as the difference of intracellular/inside charge compared to extracellular/outside charge

• outside is set as zero

  • therefore, -61.5 mV means that the inside of the cell is negative compared to outside

  • voltage is difference between the two and NOT an absolute value

What are the characteristics of resting membrane potential?

• state where there is no net current across the cell

• ALL gated channels by ion concentrations and permeability

• constant flow of K+ out and Na+ in though “leak” channels (more K+ out than Na+ in at rest)

• Na+/K+ ATPase maintains gradient (3 Na+ out, 2 K+ in)

What is repolarization?

towards resting membrane potential. Most of time that means more negative

• note-very few ions need to move across membrane to change the membrane potential (0.00003%). Most of the ions are staying put!

What are the characteristics of graded potentials?

• the stronger the stimulus, the greater the potential, the farther current flows

• happens in cytoplasm of all cells

• moves in all directions, like a ripple created by a stone tossed into pond

In cells that have voltage-gated Na+ channels, electrical (or chemical) stimulus comes along…

• Na+ permeability is changed

• Na+ moves into the cell through voltage-gated channels

• makes the inside of the cell more positive-depolarization

• but those leak channels are still there…so outflow of K+ will continue o counteract this change in potential

• unless the change is too great for the K+ leak to overcome-a threshold is reached

  • when K+ exit can not compensate for Na+ entry

What is action potential?

rapid change in membrane potential after threshold is reached

• all-or-none

  • once threshold is reached, an action potential occurs

• in a given cell, all action potentials are the same amplitude

• once threshold is reached, stronger stimuli do NOT lead to bigger action potentials

• only occur in neurons and muscle

Why do APs occur?

have voltage gated sodium channels

What are the steps of the positive feedback loop?

1. Opening of Na+ channels in the membrane

2. Increased membrane Na+ permeability

3. Increased flow of Na+ into the cell

4. Decreased membrane potential (depolarization) - Stimulus: could be a graded potential

What are absolute refractory periods?

Time between Na+ channels opening and resetting. Another AP cannot be generated

What are relative refractory periods?

AP can be generated if LARGE depolarizing stimulus came along, the threshold is high

What is the summary of nerve action potential?

1. Na+ channels open, Na+ begins to enter cell

2. K+ channels open, K+ begins to leave cell

3. Na+ channels become refractory, no more Na+ enters cell

4. K+ continues to leave cell, causes membrane potential to return to resting level

5. K+ channels closing Na+ channels reset

What are the characteristics of graded potentials?

• refers to a membrane potential, which can vary in amplitude

• can occur either due to depolarization or hyperpolarization

• may have variable signal strengths which are less than action potential

• generated by ligand-gated ion channels

• may be transmitted over short distances

• may lose strength during transmission

• two graded potentials can be added together

What are the characteristics of action potentials?

• refers to a change in the electrical potential, associated with the transmission of impulses along the membrane of a nerve cell of muscle cell

• can only occur due to depolarization

• a large depolarization, which reaches the threshold (+40 mV)

• generated by voltage-gated ion channels

• may be transmitted over long distances

• does not lose its strength during transmission

• two action potentials cannot be added together

What happens during action potential propagation?

• generated anew at each subsequent patch of membrane

• does not decrease in strength as it goes along

What is the summary of action potential propagation in unmyelinated axons?

1. at the start, the membrane is completely polarized

2. when an action potential is initiated, a region of the membrane depolarizes. As a result, the adjacent regions become depolarized

3. when the adjacent region is depolarized to its threshold, an action potential starts there

4. repolarization occurs due to the outward flow of K+ ions. The depolarization spreads forward, triggering an action potential

5. depolarization spreads forward, repeating the process

Why are action potentials generated at axon hillock?

there is a high concentration of voltage gated Na+ channels

What is the purpose for saltatory conduction?

gets rid of leak current. Oligodendrocytes and Schwann cells do not have channels

What is another way to increase propagation speed?

increase fiber diameter, myelination

What is the summary of saltatory conduction?

1. In meylinated neurons, an action potential is usually triggered at the axon hillock, just before the start of the myeline sheath. The depolarization then spreads along the axon.

2. because of myelination, the depolarization spreads passively to the next node

3. the next node reaches its threshold, and a new action potential is generated

4. this cycle is repeated, triggering an action potential at the next node

Which neurodegenerative disease is characterized by destruction of the myelin sheath?

multiple sclerosis

What happens after the AP travels through a neuron?

• must take this electrical information and transmit it to another cell

• occurs at synapses

  • electrical or chemical

• axon terminals synapse with dendrites, cell body, or axon of another neuron

What is the role of electrical synapses?

• synchronized activity of interconnected neurons

• important in fetal development (changes to chemical synapses throughout growth)

What is the role of chemical synapses?

• voltage gated calcium channel

• ligand-gated ion channel

What type of receptor is needed for Acetylcholine (ACh)?

ligand-gated ion channels (nicotinic) and GPCRs (muscarinic)

What type of receptor is needed for Norepinephrine (NE)?

GPCRs

What type of receptor is needed for Epinephrine (Epi)?

GPCRs

What are the steps for neurotransmitter receptor signaling?

1. neurotransmitter (1st messenger) binds and activates receptor

2. receptor activates G protein

3. G protein activates adenylate cyclase

4. adenylate cyclase converts ATP to cAMP (2nd messenger)

5. cAMP changes membrane permeability by opening or closing ion channels

6. cAMP activates enzymes

7. cAMP activates specific genes

What is the day in the life of a neurotransmitter?

• NTs synthesized in axon terminal

• stored in vesicles

• released from vesicles into synapse

• bind to NT Rs (pre and postsynaptic)

• presynaptic autoreceptors will regulate the subsequent release of NT from that neuron

• taken back up into presynaptic neuron (to be stored or metabolized) or degraded in synapse

What are the characteristics of neurotransmitter release?

• mediated through fusion of SNARE proteins that are activated because of increased concentrated of calcium

• they are all set to go and are waiting for the “green light”

What is the summary of synaptic transmission?

1. an action potential arrives at the presynaptic terminal bulb, resulting in a transient depolarization

2. depolarization opens voltage-gated calcium channels, allowing calcium ions to rush into the terminal

3. increasing calcium in the terminal bulb induces the secretion of some neurosecretory vesicles

4. prolonged stimulation mobilizes additional, reserve vesicles

5. neurotransmitter diffuses across the synaptic cleft to receptors on the postsynaptic cell

6. binding of neurotransmitter to the receptor alters its properties

7. channels open, letting ions flow into the postsynaptic cell. Depending on the ion, channel opening leads to either depolarization or hyperpolarization