Lecture 15

Question 1

Cell Body

Answer 1

Contains nucleus and ER of neuron

Question 2

Dendrites

Answer 2

Receives info from axon and other neuron terminals via neurotransmitter-receptor interactions

Question 3

Axon

Answer 3

Transmits signal from cell body to axon terminals (1-100 m/sec) and transports proteins and lipids to terminals with cytoskeleton

Question 4

Presynaptic Terminal

Answer 4

Synaptic Vessicles store and release neurotransmitters to activate or inhibit neurons

Question 5

What does PNS Affect?

Answer 5

All other excitable tissue: skeletal, smooth, and cardiac muscle.

Question 6

Postsynaptic Dendrites

Answer 6

Receptors bind neurotransmitters and produce ionic responses (EPSP & IPSP), act on second messenger responses, OR direct effect on ion channels (Na, K, Cl, Ca)

Question 7

Membrane Potential

Answer 7

• Potential difference between inside and outside of neuron
• -60 to -75 mV
• Ionic pumps are used on neuron to maintain internal ion concentrations
• Negatively charged components are inside cell and impermeable
• Membrane is selectively permeable to K+ ions

Question 8

Which ion establishes the resting potential?

Answer 8

K+

Question 9

Action Potential Steps (3)

Answer 9

1. Na+ open and influx to depolarize the membrane
2. Adjacent Na+ channels open and propagate the signal
3. K+ channels open and return membrane to resting potential

Question 10

Action Potential Propagation Steps (3)

Answer 10

1. Generation of Action Potential - dendrites/cell body depolarize and open voltage-sensitive Na+ channels
2. Local current flows passively down axon and open Na+ channels (action potential)
3. Continues until reaching synaptic terminal

Question 11

Refractory Period

Answer 11

• Time after action potential when Na+ channel are inactive
• Reason why action potentials don’t travel backwards
• Important in mechanism of action of some drugs like antiepileptics and antiarrhythmics

Question 12

Myelination

Answer 12

• Insulates axon - reduces Na+ leaking and increase the flow distance
• Myelin wrapped around axon by oligodendrocytes in CNS and Schwann Cells in PNS
• Nodes of Ranvier are gaps in the myelination
• Conduction velocities significantly increase with myelination (0.5-10 m/s for unmyelinated and up to 150 m/s when myelinated)

Question 13

Local Anesthesia

Answer 13

• Must enter neurons and act on open Na+ channels to prevent depolarization by blocking influx
• High potency for neurons with a high firing rate
• Binding Site: S5 & S6 transmembrane segments that wall the sodium channel pores
• Intracellular loop connecting domains III & IV creates inactivation of the sodium channels

Question 14

Lidocaine

Answer 14

Binds domain IV segment S6 portion of Na+ channel to stop neuron signals and influx.

Question 15

Molecule Characteristics + Effect on Neuron

Answer 15

Lipophilic - enters neuron (potency)

Hydrophilic - binds to site (duration of action)

Question 16

Mechanism of Antiepileptic Drugs

Answer 16

Prolongs the inactivation period of Na+ channels by increasing the refractory period and decreasing the sustained, rapid firing of neurons

Question 17

Ion-Channel Receptors - Voltage Dependent Receptors

Answer 17

• Na+ - initiation and propagation of action potential
• Ca+2 - release neurotransmitters at synapse and contract muscle tissue
• K+ - sets resting potential, hyperpolarizes tissues, alters action potential duration
• Cl- - Hyperpolarizes neurons (GABA)

Question 18

Receptor Mediated - Ligand Gated Receptors

Answer 18

• Neurotransmitters bind and control intrinsic ion channel
• Regulated by phosphorylation
• Ex: Na and Ca by glutamate and Cl by GABA

Question 19

G Protein-Coupled Receptors

Answer 19

-Bound to GTP binding proteins, adenyl cyclase, phospholipase C, or ion channels
Ex: Muscarinic cholinergic receptors, adrenergic receptors, serotonergic receptors, and peptide receptors

Question 20

Heart Example of Receptor Mediated

Answer 20

• B-Adrenergic Agonists increase calcium release

- Affect pattern of heart contraction

Question 21

Receptors + Drug Effects

Answer 21

• Determinant of quantitative relations between dose or drug concentration and pharmacological affects
• Also responsible for selectivity of drug action and mediates the actions of pharmacologic antagonist and agonists

Question 22

Receptor Affinity + Drug Effects

Answer 22

Determines drug concentration required to form significant number of drug-receptor complexes. Number of complexes could limit the maximal drug effect

Question 23

Molecules with Neurotransmitter/Neuromodulatory Properties

Answer 23

• Dopamine
• Norepinephrine
• Epinephrine
• Serotonin
• Acetylcholine
• Glutamine
• GABA

Question 24

Neurotransmitters

Answer 24

Chemical Substances that transmit nerve impulses across a synapse to postsynaptic receptor

Question 25

Catecholamines

Answer 25

- Dopamine, Norepi, Epi - CNS and P - sympathetic - NS - Work via G-proteins

Question 26

GABA

Answer 26

- IPSP (Inhibitory Postsynaptic Potentials) - Hyperpolarization - Most abundant inhibitor in CNS - Synthesized from L-glutamic acid by GAD - GABA-A receptor - increase chloride ions into neuron - GABA-B receptor - decreases calcium release

Question 27

Glutamate

Answer 27

- EPSP (Excitatory Postsynaptic Potentials) - Most abundant excitor in CNS, excitatory amino acid that has stimulatory affects and high concentrations in brain - Receptors increase sodium and calcium ion influx to depolarize neuron - PCP receptor inside channel and interacts with NMDA receptor

Question 28

Catecholamine Process

Answer 28

Synthesis >> Storage >> Release >> Receptors or Uptake >> Metabolism

Question 29

GABA-A

Answer 29

- Ligand-gated channel with alpha and beta units (react with benzodiazepines and barbiturates, BOTH INCREASE AFFINITY OF GABA FOR RECEPTOR) - GABA binding site causes Cl- influx and hyperpolarization - Benzos - bind separate from GABA site and have potentiate binding of GABA (doesn't work in its absence), antagonist = Flumazeril (Romazicon) - Barbiturates - opens Cl- channel by activating GABA directly, potentiate binding of GABA but can still work in its absence

Question 30

GABA-A Therapeutic Uses (4)

Answer 30

1. Sedative/hypnotics - Temazepam (Restoril) & Zolpidem 2. Antianxiety - Xanax 3. Antiepileptic - Phenobarbital (Luminal) 4. Muscle Relaxants - Clonazepam

Question 31

Neuromodulators

Answer 31

Affect function of neurons but doesn't act as a neurotransmitter itself.

Question 32

PCP Receptor

Answer 32

- PCP and Ketamine interact with receptor - Inhibit passage of Ca+2 and Na+ - Indirectly antagonize glutamate - Act as noncompetitive antagonists

Question 33

NMDA Receptor Roles

Answer 33

1. Long term plasticity - learning, memory, epilepsy 2. Ischemia/Hypoglycemia - induced massive release of glutamate which increases calcium concentrations and leads to cell damage or death 3. Neurological Disorders - stroke 4. Neurodegenerative diseases - Alzheimer's (treated with Memanitine [Namenda], which is a glutamate antagonist)