Lecture 15 Flashcards
Intro to Neurons
Cell Body
Contains nucleus and ER of neuron
Dendrites
Receives info from axon and other neuron terminals via neurotransmitter-receptor interactions
Axon
Transmits signal from cell body to axon terminals (1-100 m/sec) and transports proteins and lipids to terminals with cytoskeleton
Presynaptic Terminal
Synaptic Vessicles store and release neurotransmitters to activate or inhibit neurons
What does PNS Affect?
All other excitable tissue: skeletal, smooth, and cardiac muscle.
Postsynaptic Dendrites
Receptors bind neurotransmitters and produce ionic responses (EPSP & IPSP), act on second messenger responses, OR direct effect on ion channels (Na, K, Cl, Ca)
Membrane Potential
- 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
Which ion establishes the resting potential?
K+
Action Potential Steps (3)
- Na+ open and influx to depolarize the membrane
- Adjacent Na+ channels open and propagate the signal
- K+ channels open and return membrane to resting potential
Action Potential Propagation Steps (3)
- Generation of Action Potential - dendrites/cell body depolarize and open voltage-sensitive Na+ channels
- Local current flows passively down axon and open Na+ channels (action potential)
- Continues until reaching synaptic terminal
Refractory Period
- 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
Myelination
- 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)
Local Anesthesia
- 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
Lidocaine
Binds domain IV segment S6 portion of Na+ channel to stop neuron signals and influx.
Molecule Characteristics + Effect on Neuron
Lipophilic - enters neuron (potency)
Hydrophilic - binds to site (duration of action)
Mechanism of Antiepileptic Drugs
Prolongs the inactivation period of Na+ channels by increasing the refractory period and decreasing the sustained, rapid firing of neurons
Ion-Channel Receptors - Voltage Dependent Receptors
- 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)
Receptor Mediated - Ligand Gated Receptors
- Neurotransmitters bind and control intrinsic ion channel
- Regulated by phosphorylation
- Ex: Na and Ca by glutamate and Cl by GABA
G Protein-Coupled Receptors
-Bound to GTP binding proteins, adenyl cyclase, phospholipase C, or ion channels
Ex: Muscarinic cholinergic receptors, adrenergic receptors, serotonergic receptors, and peptide receptors
Heart Example of Receptor Mediated
- B-Adrenergic Agonists increase calcium release
- Affect pattern of heart contraction
Receptors + Drug Effects
- 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
Receptor Affinity + Drug Effects
Determines drug concentration required to form significant number of drug-receptor complexes. Number of complexes could limit the maximal drug effect
Molecules with Neurotransmitter/Neuromodulatory Properties
- Dopamine
- Norepinephrine
- Epinephrine
- Serotonin
- Acetylcholine
- Glutamine
- GABA
Neurotransmitters
Chemical Substances that transmit nerve impulses across a synapse to postsynaptic receptor
Catecholamines
- Dopamine, Norepi, Epi
- CNS and P - sympathetic - NS
- Work via G-proteins
GABA
- 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
Glutamate
- 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
Catecholamine Process
Synthesis»_space; Storage»_space; Release»_space; Receptors or Uptake»_space; Metabolism
GABA-A
- 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
GABA-A Therapeutic Uses (4)
- Sedative/hypnotics - Temazepam (Restoril) & Zolpidem
- Antianxiety - Xanax
- Antiepileptic - Phenobarbital (Luminal)
- Muscle Relaxants - Clonazepam
Neuromodulators
Affect function of neurons but doesn’t act as a neurotransmitter itself.
PCP Receptor
- PCP and Ketamine interact with receptor
- Inhibit passage of Ca+2 and Na+
- Indirectly antagonize glutamate
- Act as noncompetitive antagonists
NMDA Receptor Roles
- Long term plasticity - learning, memory, epilepsy
- Ischemia/Hypoglycemia - induced massive release of glutamate which increases calcium concentrations and leads to cell damage or death
- Neurological Disorders - stroke
- Neurodegenerative diseases - Alzheimer’s (treated with Memanitine [Namenda], which is a glutamate antagonist)
