Handout 3



Chapter 4

Electrical to Chemical Signal to Electrical/Psychopharmacology

The players:

a) Ion channels:

1) Signals that __transduce__ (change from one signal type to another)

a) Ligand Gated

a. Ligand = a chemical that attaches to a binding site on a receptor

b. Found in dendrites, cell body and axon terminal

b) Mechanically Gated

a. Found in sensory systems (example: skin)

2) Signals that ___propogate___

c) Voltage Gated

a. Found all throughout neuron membrane

b. Propagate post-synaptic potentials and action potentials

b) Receptors:

| |NT receptor location? |Directly/indirectly opens |Speed of action? |Length of action? |

| | |channel? | | |

|Ionotropic (ligand receptor) |On channel |Directly |Fast |Short |

| | |- via NT | | |

|Metabotropic (g protein coupled receptor)|Coupled to G-protein |Indirectly |Slow |Long |

| | |- via alpha subunit | | |

c) Neurotransmitters; their lifecycle:

1. Biosynthesis

a. Differs for each neurotransmitter but each begins with precursor + enzyme = NT

2. Storage

a. Vesicles are created in the golgi apparatus

b. Precursors, enzymes, and vesicles are transported down the axon to the terminal (microtubules)

c. Once in the terminal, NT are synthesized and packaged into vesicles

3. Release (See below)

4. Receptors [See above (iono vs. metabotropic) ]

5. Inactivation

a. Destruction (enzymes break NT down)

b. Diffusion (the process by which molecules spread from areas of high concentration, to areas of low concentration)

c. Reuptake (by presynaptic receptors). For a picture: pg. 61

c.2) For specific neurotransmitters, see chart below

d) Regulation of axon terminal activity (how does a neuron know its fired too much or too little)

1. Autoreceptor:

a. Definition: Metabotropic receptors on the presynaptic neuron that respond to the neurotransmitter that they themselves release

b. Purpose: to regulate the synthesis and release of the neurotransmitter; mostly inhibitory effects that is the presence of that NT causes a decrease in the rate of synthesis or release of the NT

c. Picture: pg. 113, more information in chapter 2 pg. 63

2. Heteroreceptor:

a. Definition: Activation of neuron 1’s terminal button causes presynaptic inhibition OR facilitation of the neuron 2’s terminal button. The second neuron contains heteroreceptors that are sensitive to the NT released by neuron 1.

b. Purpose: also to regulate synthesis and release of neurotransmitter possibly through regulating Ca++

c. Example: Endorphins, Picture: pg. 113

3. Retrograde signaling

a. Definition: Post-synaptic cell sends messengers back to the presynaptic cell

b. Example: If a post-synaptic neuron is receiving too much input, they may snip off a NT like 2-AG which resides in the cell membrane of the post-synaptic neuron. The 2-AG NT will float back to the pre-synaptic cell and bind to CB1. CB1 will slow down the entry of Ca++ to the cell.

The Game Plan

WHAT? ACTION?

1. Action potential arrives at the ___terminal button_____

2. Na+ influx causes opening of voltage-dependent/gated __Ca++__ channels

3. Ca++ influx severs __anchoring proteins__ and causes vesicles to fuse with pre-

synaptic membrane

4. Vesicles release NT via __exocytosis__

5. NT diffuses across synaptic cleft

6. Receptors bind NT

7. Ion channels open

8. Ions move

9. Membrane potential changes (__EPSP__ if depolarized, __IPSP__ if hyperpolarized)

10. EPSP and IPSP summate

11. Membrane potential reaches threshold

12. Action potential propagates

Psychopharmacology (routes of administration of drugs and their fate in the body) [i.e. Big picture]

- Psychotropics: drugs affecting perception, mood and behavior

- Pharmacokinetics: the process by which drugs are absorbed, distributed, metabolized, and excreted within the body

o Administration:

▪ Injection (in muscles, underneath the skin, veins and more)

▪ Oral (sublingual, inhalation)

▪ Topical (directly into the skin, steroids)

o Measurement:

▪ Blood plasma

▪ Microdialysis

o Distribution:

▪ Properties that affect absorption

• Lipid solubility: molecules that are lipid soluble pass through cells easily & quickly

• pH

▪ Impediments to drugs

• MAO in gut (will break down monoamines and inactivate certain NT)

• Depot binding

o Blood albumin: if the molecule is bound to a depot (like albumin) they cannot reach their sites of action

o Fat cells: another example, most slowly, and less likely to interfere with the initial effects of the drug

▪ Blood brain barrier: only lets fat soluble molecules pass; the faster a drug can get pass this the better the “high”

- Psychodynamics: effect the drug exerts

Drug Effectiveness

-How to measure?

Dose Response Curve:

[pic] [pic]

Sites of Action: What are the many ways drugs can affect you?

|Agonist |Antagonist |Inverse Agonist |

|-chemical that facilitates post-synaptic effects |-chemical that block or inhibit post-synaptic effects |-chemical that binds to the receptor site of an |

|-example: AChE (acetylcholinesterase) breaks down ACh.|-example: a choline reuptake blocker would prevent |agonist but reverses the activity of the receptor |

|In a patient with ACh deficit, can block enzyme so |choline from re-entering the cell thereby preventing |-example: if a zinc ion binds with the zinc binding |

|that ACh can continually stimulate a post-synaptic |the re-synthesis of ACh |site on an NMDA receptor, the activity of that |

|cell. So a chemical that blocks AChE is a ACh agonist.| |receptor is decreased |

Drugs can be either:

|Indirect |Direct |

|-chemical that binds to a receptor site other than the primary receptor site or |-chemical that binds directly to the primary binding site and directly affects |

|indirectly affects the effectiveness of a drug |the effectiveness of a drug |

|-example: benzodiazepines promote the activity of the GABAa receptor and |-example: muscimol binds to the GABA binding site and serves as a direct agonist.|

|therefore is an indirect agonist | |

|Non-competitive binding |Competitive binding |

|-a receptor has a separate neuromodulator binding site. The molecule does not |-drug binds at the exact same receptor site as a neurotransmitter |

|compete with molecules of |-example: direct agonist |

|-example: GABAa has a separate receptor for specific drugs (benzodiazepine) | |

|NT |E/I |Precursor |Receptor type |Inactivation |Function |Brain pathway |

|Amino acids | | | | |Sensory motor |Everywhere |

|Glutamate |+ |Glutamine |I: NMDA, AMPA, kainate |Reuptake |Direct excitatory effects in brain and |Cortex ( cortex |

| | |Byproduct of Krebs |M: metabotropic glu receptor | |spinal cord raise or lower the | |

| | | | | |threshold of excitation affecting the | |

| | | |[NMDA: 6 binding sites: (glu, gly, polyamine, zinc, | |rate of action potentials | |

| | | |mg, PCP), also known as an AND gate= will only open | | | |

| | | |if there is depolarization and glu binds] | | | |

|GABA |- |Glutamate |I: GABAa (controls Cl-) |Reuptake |Direct inhibitory effects throughout |Cortex ( cortex |

| | | |M: GABAb (controls K+) | |brain and spinal cord | |

| | | | | | | |

| | | |[GABAa, at least 5 binding sites: (GABA, | | | |

| | | |benzodiazepine, steroid, picrotoxin, barbiturate) | | | |

|Biogenic amines | | | | |Modulatory |Midbrain ( Cortex |

|Acetylcholine (ACh) |+ |Choline & |I: nicotinic; in skeletal muscles |-AChE |-Primary NT secreted by efferent axons |-Basal forebrain ( |

| | |Acetyl CoA |-agonized by: nicotine |(acetylcholinesteras|in CNS and 1st discovered |-Medial septum ( |

| | | |-antagonized by: curare |e), eventual |-Help learning (basal) |-Pons ( |

| | | |M: muscarinic; in smooth muscle |reuptake of choline |-Form memories (medial) | |

| | | |-agonized by: muscarine | |-REM sleep (pons) | |

| | | |-antagonized by: atropine | | | |

|Norepinephrine (NE) |+ |Tryosine ( L-DOPA( |M: α1 & β1-2 (post-syn, excitatory) |Reuptake, MAO |-Arousal |Locus coeruleus (dorsal pons) ( EVERYWHERE! |

|Catecholamine |(genera|Dopamine(NE |α1 (autoreceptor, inhibitory) |(monoamine oxidase) |-Attention | |

| |l) | | | |-Increases vigilance | |

|Dopamine (DA) | |Tyrosine (AA) ( |M: |Reuptake, MAO |-Movement |-Nigrostriatal pathway: |

|Catecholamine |+ |L-DOPA |D1 (post-synaptic) | | |Substantia nigra ( striatum (BG) |

| |- | |D2 (pre & post-synaptic) | |-Working mem/planning |-Mesocortical: VTA( Cortex |

| | | | | | |-Mesolimbic: VTA ( Limbic |

| | | | | |-Reinforcement/addiction | |

|Serotonin |+ |Tryptophan |9 types |Reuptake, MAO |-Mood, social cognition |Raphe nucleus (in pons, midbrain, medulla) ( |

|(5-HT) | | |All metabotropic but 1 | |-Suppresses certain categories of |cortex, basal ganglia, hippocampus |

|Indolamine | | | | |species-typical behavior | |

|Neuropeptides/ Opioids |- |Amino acids |3 all Metabotropic: |Enzymes (no |-Act as both NT and NM |-Used in combination with other NTs |

|(ex. Endorphins) | | |mu: most analgesic effects |reuptake) |-Modulation of effects of other NT |-Everywhere, esp. limbic |

| | | |delta: some analgesic effects | | | |

| | | |kappa: negative side effects | | | |

-----------------------

Therapeutic Index: ratio of a lethal dose to effective dose:

High therapeutic index ratio = drug relatively safe (because you need a lot of the drug for it to be lethal)

Low therapeutic index ratio: BE CAREFUL.

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download