NEUROCHEMISTRY & NEUROTRANSMITTERS

NEUROCHEMISTRY &NEUROTRANSMITTERS

NEUROCHEMISTRY IS A SUB-SPECIALTY OF BIOCHEMISTRY THAT DEVELOPED RAPIDLY IN THE 1950’S. IT DEALS PRIMARILY WITH THE CHEMISTRY OF THE BRAIN AND NERVOUS SYSTEM. A VERY IMPORTANT PART OF THIS DISCIPLINE DEALS WITH SO-CALLED “NEUROTRANSMIT- TER SUBSTANCES” WHICH ARE SIGNALING CHEMICALS SENT BETWEEN NERVE & NERVE AND NERVE & MUSCLE. THESE SUBSTANCES ARE CLOSELY RELATED TO HORMONES. OTTO LOEWI

ANOTHER WAY OF LOOKING AT HORMONES, NEUROTRANMITTERS • AND RELATED MOLECULES IS SIMPLY TO LABEL THEM AS SIGNALLING • DEVICES,BUT THAT IS A BIT OF AN OVERSIMPLIFICATION. • OUTLINE: • REVIEW OF NERVOUS SYSTEM; TRANSMISSION • GATED PROTEINS OF NERVOUS TRANSMISSION • THE PRESYNAPTIC AREA OF NEURONS • NEUROTRANSMITTERS & SYNTHESIS • THE SYNAPTIC AND POSTSYNAPTIC AREAS • RECEPTOR PROTEINS • SURVEY OF NEUROTRANSMITTER DISEASES • THIS IS AN INTRODUCTION TO NEUROLOGY • & PHARMACOLOGY.

WHAT DO WE REMEMBER FROM UNDERGRADUATE STUDIES ABOUT COMPONENTS & FUNCTIONS OF THE NERVOUS SYSTEM? (REVIEW OF THE NERVOUS SYSTEM & NEUROTRANSMISSION) NERVE (aka NEURON) IS A CELL TYPE THAT COMMUNICATES INFORMATION BY ELECTRICAL AND CHEMICAL MEANS. THE INFORMATION, TYPICALLY (BUT WITH EXCEPTIONS), TRAVELS FROM THE DENDRITE THROUGH THE CELL BODY AND THE AXON TO THE AXON TERMINALS. JUST LIKE HORMONES, THE COMMUNICATION (OR SIGNALLING) IS MEANT TO COORDINATE THE ACTIONS OF HIGHER ORGANISMS, BUT IN A MUCH MORE RAPID MANNER THAN IS COMMON TO HORMONES. TYPICALLY THE RATE OF NERVE CONDUCTION TAKES PLACE AT 1 TO 100 meters/ second FOR UNMYELINATED NERVES [WE’LL TAKE UP THE SUBJECT OF MYELINATION A LITTLE LATER]. THE RATE OF CONDUCTION ALSO INCREASES WITH THE DIAMETER OF THE NEURON ITSELF.

1) NEURONS SERVE THE CNS 2) SEVERAL KINDS ARE REQUIRED

IN ORDER TO OPERATE THE COMPLETE NERVOUS SYSTEM, OTHER NEURON TYPES ARE NECESSARY – SUCH AS MOTOR & SENSORY NEURONS. WHILE THE MOTOR NEURON SENDS SIGNALS TO MUSCLES, THE SENSORY NEURON TRANSDUCES SIGNALS SUCH AS HEAT AND PAIN INTO SIGNALS AND SENDS THEM TO THE BRAIN. THE IMPORTANT DIFFERENCE IN THESE NERVES IS THE PRESENCE OF MYELINATION.

THE CONDUCTION PROPERTIES OF NERVES - IN AN UNMYELINATED NERVE, AT REST, THE POTENTIAL ACROSS THE NERVE MEMBRANE IS ~ -60mV. WHEN A WAVE OF DEPOLARIZATION TRAVELS DOWN THE NERVE, THE NERVE POTENIAL INCREASES TO ~ +30mV, THEN RAPIDLY HYPERPOLARIZES BEFORE RETURNING TO THE RESTING POTENTIAL IN ABOUT 3.8 msec. THIS IS ACCOMPANIED BY TWO EVENTS AT THE NEURAL MEMBRANE, 1st AN INCREASE IN Na ion PERMEABILITY, THEN AN INCREASE IN K ion PERMEABILITY. WHAT CAUSES THESE EVENTS?

REMEMBER THAT, NORMALLY, POTASSIUM IS HIGHER IN CONCENTRATIION INSIDE THE CELL WHILE SODIUM IS HIGHER OUTSIDE THE CELL. ANY CHANGE IN MEMBRANE PERMEABILITY SPECIFIC FOR THESE IONS WILL CAUSE THEM TO FLOW INWARD FOR SODIUM – OUTWARD FOR POTASSIUM. IF SODIUM IS ALLOWED TO FLOW INWARD, THE POTENTIAL BECOMES MORE POSITIVE. IF POTASSIUM IS ALLOWED TO FLOW OUTWARD, THE POTENTIAL BECOMES MORE NEGATIVE. THE FLOW IS CONTROLLED BY “GATED” ION CHANNEL PROTEINS. THESE MEMBRANE PROTEINS ARE AFFECTED BY LOCAL VARIATIONS IN ION CONCENTRATION AND POTENTIAL. SODIUM CHANNEL PROTEIN = -60mV (negative inside)

THE STRUCTURE AND OPERATION OF THE POTASSIUM GATED CHANNEL • PROTEIN IS SIMILAR TO THAT OF THE SODIUM GATED CHANNEL PROTEIN • WITH SOME ESSENTIAL DIFFERENCES: • THERE IS A MOLECULAR FILTER THAT PREVENTS THE PASSAGE OF • SMALLER SODIUM IONS THROUGH THE CHANNEL. WHY IS SUCH A • FILTER NOT NECESSARY FOR SODIUM GATED CHANNEL PROTEINS? • THE OPENING OF THE POTASSIUM GATED CHANNEL IS DELAYED IN • TIME BY THE LOCAL VOLTAGE CHANGES SO THAT: AS THE POTASSIUM • CHANNEL STARTS TO OPEN, THE SODIUM CHANNEL STARTS TO CLOSE. • SODIUM CHANNEL TOXINS: • TETRODOTOXIN • (puffer fish) AND SAXITOXIN (plankton species) • BIND WITH HIGH SPECIFICITY TO SODIUM • CHANNELS (KD = <1 nM). THESE ARE USED • IN RADIOACTIVE FORMS TO PURIFY SODIUM • CHANNEL PROTEINS AND MAP THEIR • LOCATIONS ON AXONS. SAXITOXIN IS FOUND • IN SOME FORMS OF THE “RED TIDE” FAMILIAR • TO PEOPLE WHO LIVE ALONG SEA COASTS. SAXITOXIN

LOOKING AT THE ACTION POTENTIAL IN MOTION: THIS SHOWS HOW THE ACTION POTENTIAL MOVES ALONG THE AXON WITH TIME. THE OPENING AND CLOSING OF GATED CHANNEL PROTEINS IS ONLY SHOWN FOR Na+ IONS FOR SIMPLICITY. HYPERPOLARIZATIOIN GUARANTEES THAT THE WAVE OF DEPOLARIZATION IS UNIDIRECTIONAL. AT TIME = 0 (e. g., WHEN ACTIVATED BY A STIMULUS) A GIVEN AREA (DISTANCE) OF MEMBRANE IS IMMEDIATELY DEPOLARIZED. TIME = 0 TIME = 1 ms TIME = 2 ms

MYELINATION: WHAT IS IT AND WHAT DOES IT DO? MYELINATION IS THE ADDITION OF CONCENTRIC PLASMA MEMBRANES AROUND THE REGULAR PLASMA MEMBRANE OF A NEURON. THE MYELIN IS PRODUCED BY A GLIAL CELL KNOWN AS A SCHWANN CELL. MYELIN SHEATH NODES OF RANVIER MYELIN LAYERS AXON NOTE THAT THE SHEATHS ARE SEPARATED BY SHORT NON-MYELINATED SPACES. SCHWANN CELL THE COMPOSITION OF THE MYELIN LAYERS IS SIMILAR IN LIPID TYPES TO THOSE OF THE PLASMA MEMBRANE. HOWEVER, 2 PROTEINS ARE UNIQUE TO THE MEMBRANE: (PO IN THE PNS) AND PROTEOLIPID (IN THE CNS). THE ROLE OF THESE PROTEINS IS TO BIND TO THEMSELVES AND HOLD THE LAYERS TOGETHER.

MYELINATED NERVES HAVE THE ADVANTAGE OF ALLOWING CONDUCTION TO OCCUR AT 10x THE RATE OF UNMYELINATED NERVES. THIS IS VERY IMPORTANT FOR COMMUNICATING WITH MUSCLES (FROM THE CNS) AND SIGNALLING THE RECEPTION OF PERIPHERAL PAIN, PRESSURE, ETC. (TO THE CNS). SINCE THE VELOCITY OF NERVE CONDUCTION IS PROPORTIONAL TO NERVE CROSS SECTION, IT ALSO MYELINATED NERVES ALLOW THE EXISTENCE OF THINNER NERVES. FOR EXAMPLE, A 12 mm DIAMETER MYELINATED NERVE WILL CONDUCT AT A RATE OF 12 m/s. THE COMPARABLE CONDUCTING UNMYELINATED NERVE MUST BE 600 mm IN DIAMETER. IN PRACTICAL TERMS, WE WOULD HAVE TO HAVE SPINAL CHORDS AS THICK AS TREE TRUNKS TO CARRY OUT OUR NORMAL, HUMAN NEUROLOGICAL FUNCTIONS! myelinated unmyelinated

HOW MYELINATED NEURONS WORK: • MYELINATED NEURONS CONDUCT BY THE PROCESS OF SALTATORY • (LATIN – SALTARE “TO JUMP”) DEPOLARIZATION. IN THE MYELINATED • NEURON, NEARLY ALL OF THE SODIUM ION GATED CHANNEL PROTEINS • ARE LOCATED AT THE NODES OF RANVIER. CONSEQUENTLY, DEPOLARI- • ZATION OCCURS AT THE NODES AND JUMPS FROM NODE TO NODE AT • A HIGHER RATE THAN SIMPLE DEPOLARIZATION ON AN UNMYELINATED • NERVE. • CONCENTRATED VOLTAGE • GATED Na+ CHANNELS • DEPOLARIZE A LOCAL AREA. • DEPOLARIZATION MOVES • RAPIDLY DOWN THE INSIDE • OF THE AXON (JUMPS) TO • THE NEXT NODE. • AT THE NEXT NODE, THE • CHANNELS OPEN AND • CAUSE THE NEXT WAVE OF • DEPOLARIZATION.

THE PRESYNAPTIC AREA • WITH THE ARRIVAL OF THE DEPOLARIZED SIGNAL AT THE PRESYNAPTIC • AREA A NUMBER OF EVENTS OCCUR THAT MUST BE CONSIDERED • SEPARATELY AND TOGETHER : • THE TRANSDUCTION OF THE SIGNAL IN THIS AREA • THE SYNTHESIS OF NEUROTRANSMITTERS • THE MECHANISM(S) OF TRANSMITTER RELEASE • THE KINDS OF NEUROTRANSMITTERS THAT EXIST • HOW A SUBSTANCE CAN “QUALIFY” AS A NEUROTRANSMITTER • THE SEQUENCE OF EVENTS THAT CAUSE TRANSMITTER RELEASE

ARRIVAL AT THE SYNAPSE • WITH THE ARRIVAL OF THE DEPOLARIZED SIGNAL AT THE SYNAPSE • A NUMBER OF EVENTS OCCUR THAT MUST BE CONSIDERED SEPARATELY • AND TOGETHER : • THE TRANSDUCTION OF THE SIGNAL • THE SYNTHESIS OF NEUROTRANSMITTERS • THE MECHANISM(S) OF TRANSMITTER RELEASE • THE KINDS OF NEUROTRANSMITTERS THAT EXIST • HOW A SUBSTANCE CAN “QUALIFY” AS A NEUROTRANSMITTER • THE SEQUENCE OF EVENTS THAT CAUSE TRANSMITTER RELEASE

THE PRESYNAPTIC AREA (aka AXON TERMINAL) IS A VERY BUSY LOCATION. THE ELECTRON MICROGRAPH SHOWS THE PRESENCE OF MANY VESICLES AND FIBERS. THE AREA IS TYPICALLY WIDER THAN THE AXON TO FACILITATE RAPID COMMUNICATION WITH THE POSTSYNAPTIC CELL. WHEN THE WAVE OF DEPOLAR- ZATION ARRIVES AT THIS AREA, Ca+2 IONS PLAY AN IMPORTANT DOUBLE ROLE IN THE TRANSDUCTION OF THE SIGNAL THAT CAUSESTHE RELEASE OF NEUROTRANSMITTERS. DEPOLARIZATION AT THIS POINT CAUSES THE OPENING OF VOLTAGE GATED Ca+2 CHANNEL PROTEINS.

THE FIGURE SHOWS TWO STAGES • OF THE ROLE OF Ca+2 IN THIS • PROCESS. • THE Ca+2 CHANNEL PROTEIN • (GREEN) IS CLOSED WITH • HIGHER CONCENTRATIONS OF • Ca+2 IN THE SYNAPTIC CLEFT. • UPON DEPOLARIZATION, THE • CHANNEL PROTEIN OPENS AND • ADMITS Ca+2 (RED DOTS) TO THE • PRESYNAPTIC CYTOPLASM. THIS • CAUSES: 1. TRANSPORT OF THE • SYNAPTIC VESICLE TO THE • SYNAPTIC MEMBRANE, FUSION & • 2. OPENING OF THE SYNAPTIC • VESICLE TO THE SYNAPTIC CLEFT. • NOTE: A NUMBER OF PRESYNAPTIC • PROTEINS ARE INVOLVED IN • THIS TRANSPORT AND FUSION • PROCESS. SYNAPTIC CLEFT SYNAPTIC CLEFT

THE SYNTHESIS OF NEUROTRANSMITTERS AND THEIR STORAGE TAKES PLACE IN THE PRESYNAPSE. EVEN THOUGH WE HAVE NOT YET CONSIDERED NEUROTRANSMITTERS -- EXCEPT TO SAY THAT THEY ARE BIOCHEMICALS THAT CONVEY SIGNALS FROM NEURON TO NEURON OR NEURON TO MUSCLE – LET’S LOOK AT THE SYNTHESIS OF TWO COMMON NEUROTRANSMITTERS: ACETYLCHOLINE AND NOREPINEPHRINE. ACETYLCHOLINE IS MADE FROM ACETYL-CoA AND CHOLINE (DIETARY SOURCE): THE SYNTHESIS IS ENTIRELY WITHIN THE PRESYNAPTIC CYTOPLASM.

BELOW YOU SEE THE DIAGRAM OF SYNTHESIS AND STORAGE OF ACETYLCHOLINE NOTE: THE REUSE OF THE SYNTHETIC BIOCHEMICALS – ACETYL CoA AND CHOLINE. AFTER SYNTHESIS, THE NEUROTRANSMITER IS TAKEN UP INTO THE PRESYNAPTIC VESICLE AND THE VESICLE IS USUALLY TAKEN TO THE VICINITY OF THE PRESYNAPTIC TERMINAL (OR MEMBRANE). EACH VESICLE CONTAINS ABOUT 10,000 ACETYLHOLINE (Ach) MOLECULES.

THE SYNTHESIS OF NEUROEPINEPHRINE • IS MORE COMPLEX. • NOTE THE FOLLOWING: • THE SYNTHESIS MAY CONTINUE ON TO • EPINEPRINE. IT BEGINS WITH TYR. • NOREPINEPHRINE IS USUALLY A NT • WHILE EPINEPHRINE IS A HORMONE – • THE ROLES MAY BE REVERSED. • TYROSINE HYDROXYLASE IS THE • RATE LIMITING ENZYME. • AROMATIC AMINO ACID DECARBOXYLASE • IS AN ENZYME IN THE PATHWAY OF OTHER • NT SYNTHESES (PINK SQUARE). • DOPAMINE IS FORMED IN THE CYTOPLASM • AND THEN ENTERS THE VESICLES FOR THE • FINAL REACTION(S). • *DOPA = 3,4-DIHYDROXYPHENYLALANINE. *

SO FAR WE KNOW THAT Ca+2 IONS INDUCE THE TRANSPORT AND FUSION OF VESICLES CONTAINING NEUROTRANSMITTERS TO THE PRESYNAPTIC MEMBRANE THAT BORDERS THE SYNAPSE. WHAT HAPPENS NEXT? A REFERENCE WAS MADE TO PROTEINS THAT ARE PROMPTED BY Ca+2 IONS TO CAUSE FUSION OF VESICLES & PRE-SYN. MEMBRANES. THIS IS ACCOMPLISHED WITH A PROTEIN COMPLEX OF SYNTAXIN- SYNAPTOBREVIN-SNAP25 MOLECULES. THESE MOLECULES HAVE BEEN PROPOSED TO ALSO CONTINUE IN THE FORMATION OF PORES IN THE FUSED MEMBRANES EITHER BY “FULL COLLAPSE” OR “KISS- AND-RUN” MECHANISMS. THE FULL COLLAPSE MECHANISM CAUSES THE COMPLETE EMPTYING OUT OF THE NTs IN THE VESICLE. THE KISS AND RUN MECHANISM FORMS A TRANSIENT HOLE AND THEN CLOSES LEAVING SOME OF THE NTs IN THE VESICLE. THE VARIATION ALLOWS FOR CONTROL IN THE AMOUNT OF NT RELEASED INTO THE SYNAPTIC CLEFT.

SNAP-25 SYNTAXIN SYNAPTOBREVIN SNAP = Synaptosome associated protein is Ca+2 ion sensitive (25kD) SYNTAXIN = 35 kD SYNAPTOBREVIN = ~19 kD PROTEIN COMPLEX AT THE FUSED MEMBRANES FORCING THE MEMBRANES OPEN AS A RESULT OF Ca+2 BINDING.

NEUROTRANSMITTER S ARE RELATIVELY SIMPLE, SMALL MOLECULES PARTIAL LIST: CHOLINERGIC – e. g., ACETYLCHOLINE CATECHOLAMINES – e. g., NOREPINEPHRINE AMINO ACID/DERIVATIVES – e. g. GLYCINE, g-AMINOBUTYRIC ACID SOME HORMONES- e.g., EPINEPHRINE NEUROMODULATORS- e.g. ENDORPHINS (NOT TRUE NTs) NOTE THAT ONE END OF THE MOLECULE HAS A POSITIVE CHARGE

THIS IS A GENERAL LIST THAT INVESTIGATORS HAVE COME TO • AGREE UPON FOR A SUBSTANCE TO BE CONSIDERED AS A • NEUROTRANSMITTER: • SUBSTANCE MUST BE PRESENT IN THE PRESYNAPSE. • SUBSTANCE MUST BE RELEASED WITH NEURAL STIMULATION. • EFFECTS OF SUBSTANCE, WHEN APPLIED TO A POSTSYNAPTIC • AREA, MUST BE IDENTICAL TO THE PHYSIOLOGICAL EVENT • CAUSED BY THE PRESYNAPTIC DEPOLARIZATION. • THE EFFECTS MUST BE PHYSIOLOGICALLY PROPORTIONAL TO • THE PRESYNAPTIC STIMULUS. • THERE MUST BE A LOCAL MECHANISM TO INACTIVATE THE • SUBSTANCE. • EXPERIMENTALLY SOME OF THESE CONDITIONS ARE DIFFICULT TO • OBTAIN DATA FOR.

A QUICK REVIEW AND LEAD IN TO WHAT OCCURS AT THE POSTSYNAPSE WHAT WE NOW WANT TO COVER ARE A FEW DETAILS ABOUT THE SYNAPSE, RECEPTORS AND INACTIVATION

THE SYNAPTIC CLEFT THE SYNAPTIC CLEFT IS A COMPARTMENT THROUGH WHICH NEUROTRANSMITTERS TRAVEL FROM THEIR RELEASE AT THE PRESYNAPSE TO A RECEPTOR AT THE POSTSYNAPTIC MEMBRANE. THE NTs MOVE BY DIFFUSION TAKING ABOUT ½ msec TO ARRIVE AT THEIR RECEPTORS. AFTER BINDING TO THEIR RECEPTORS, NTs MAY BE ENZYMATICALLY BROKEN DOWN (e.g. ACETYLCHOLINE BY THE ACTION OF ACETYLCHOLINESTERASE) OR TAKEN BACK UP AGAIN BY THE PRESYNAPSE (e.g. NOREPINEPHRINE IS TAKEN BACK UP BY A TRANSPORT PROTEIN). VESICLE PRESYNAPSE POSTSYNAPSE FROG NEUROMUSCULAR SYNAPTIC CLEFT. CLEFTS ARE TYPICALLY ~200 ANGSTROMS WIDE.

POSTSYNAPTIC RECEPTOR PROTEINS THE RECEPTORS THAT BIND WITH NEUROTRANSMITTERS MAY BE DIVIDED INTO TWO MAIN FAMILIES AND SERVERAL SUB-FAMILIES: VOLTAGE GATED CATION Na+ CHANNELS (e.g. ACETYLCHOLINEM ) (USE G PROTEINS) K+ CHANNELS (e.g. THE SAME) Ca+2 CHANNELS TRANSMITTER GATED ION ACETYLCHOLINEN CATION ex (LIGAND GATED) GLUTAMATE GATED Ca+2 ex SEROTONIN GATED CATION ex gABA GATED Cl-in GLYCINE GATED Cl- in IN ADDITION, ACETYLCHOLINE RECEPTORS ARE ALSO DIVIDED INTO TYPES THAT ALSO BIND TO EITHER NICOTINE OR MUSCARINE:

IF WE CONSIDER ACETYLCHOLINE, IT WILL BIND TO EITHER A NICOTINIC OR A MUSCARINIC RECEPTOR. A NICOTINIC RECEPTOR HAS THE APPEARANCE SHOWN HERE: THIS RECEPTOR OPENS A PASSAGE (HOLE) FOR Na+ ENTRY. NICOTINE ALSO BINDS TO THE RECEPTOR. THIS TYPE OF RECEPTOR IS FOUND ON MUSCLE TISSUES (NEUROMUSCULAR JUNCTION).

TWO RATHER WELL-KNOWN SUBSTANCES: CURARE AND COBRATOXIN ALSO BIND TO THE NICOTINIC ACETYLCHOLINE RECEPTOR TO CAUSE PARALYSIS. ORIGINALLY, CURARE WAS PLACED ON ARROWS AND DARTS FOR HUNTING. IT KILLED ANIMALS BY PARALYSIS OF LUNG MUSCLES. THE WORD IS DERIVED FROM THE SOUTH AMERICAN INDIAN WORD: WOORARI “POISON”.

MUSCARINIC ACETYLCHOLINE RECEPTORS MAKE USE OF G PROTEINS TO ACHIEVE A POSTSYNAPTIC EFFECT WHICH MAY CAUSE DEPOLARI- ZATION OR HYPERPOLARIZATION (INHIBITION). HERE IS AN EXAMPLE OF ONE RECEPTOR THAT CAUSES HYPERPOLARIZATION. AFTER ACETYLCHOLINE BINDS TO THE RECEPTOR IT ACTIVATES A G PROTEIN (TOP PICTURE). IN THIS CASE THE G subg and subb SUBUNITS (RATHER THAN THE suba subunit) DIFFUSE TO A POTASSIUM CHANNEL PROTEIN AND CAUSE IT TO OPEN. THIS CAUSES K+ TO FLOW OUT OF THE POSTSYNAP- TIC CELL AND HYPER- POLARIZE (IT BECOMES MORE NEGATIVE AS SHOWN ON THE BOTTOM). THIS IS A MECHANISM USED IN HEART TISSUE TO SLOW DOWN THE HEART RATE.

AN EXAMPLE OF TREATING PARKINSON’S DISEASE BY USING NEUROTRANSMITTER REPLACEMENT – ALLEVIATING NEUROPATHOLOGY PARKINSON’S DISEASE AFFECTS PATIENTS BY ADVERSLY AFFECTING VOLUNTARY MOVEMENT (e.g. WALKING) AND PRODUCING INVOLUNTARY TREMOR. THE DISEASE IS RELATED TO A DEGENERATION OF NEURONS THAT PRODUCE DOPAMINE AS A NEUROTRANSMITTER (SEE THE SYNTHETIC PATHWAY FOR NOREPINEPHRINE). THESE PATIENTS CAN BE TREATED WITH AN AGONIST (REPLACEMENT THAT STIMULATES THE DOPAMINE RECEPTOR) KNOWN AS BROMOCRIPTINE. THIS IS AN ARTIFICIAL WAY OF SUPPLEMENTING THE LOSS OF DOPAMINE IN THE CNS THAT IS NEEDED FOR NORMAL MOTOR (MUSCLE) FUNCTIONS.

WHAT IS IMPORTANT TO KNOW? • THE CONDUCTION PROPERTIES OF UNMYELINATED AND MYELINATED • NERVES. • HOW DOES A GATED SODIUM CHANNEL PROTEIN WORK? • WHAT ARE SODIUM CHANNEL TOXINS? (WHAT DO THEY DO?) • WHY WOULD OUR SPINAL CHORDS BE AS BIG AS TREE TRUNKS • WITHOUT MYELINATED NERVES? • WHAT HAPPENS IN THE PRESYNAPTIC AREA TO VESICLES WHEN • CALCIUM CHANNELS OPEN? • WHAT IS DOPA? WHAT DO NOREPINEPHRINE AND EPINEPHRINE • HAVE IN COMMON? • WHAT IS A “KISS AND RUN” MECHANISM FOR VESICLE OPENING? • WOULD YOU CONSIDER ENDORPHINS TO BE NEUROTRANSMITTERS • ACCORDING TO THE CRITERIA THAT QUALIFY SUBSTANCES TO BE NTs? • WHAT ARE THE TWO GENERAL KINDS OF ACETYLCHOLINE RECEPTORS • AND WHAT MECHANISM DO THEY USE TO ACHIEVE A POSTSYNAPTIC • EVENT (EFFECT)? • 10) WHAT IS BROMOCRIPTINE AND WHY IS IT USED?

NEUROCHEMISTRY & NEUROTRANSMITTERS