MCB C61 Midterm 1

categories of NT

Amino acid neurotransmitters: glutamate and glycine and GABA Neurotransmitters made directly from amino acids: serotonin, dopamine, norepinephrine, epinephrine, histamine Acetylcholine Polypeptide neurotransmitters: neuropeptides, endorphins

refractory period

After the voltage-gated Na+ and K+ open and close, they require several milliseconds to return to a state that can be triggered again to open. prevents signal in 2 directions

acetylcholine

Is produced and released by a relatively small number of neurons clustered into several regions deep in the brain's interior called the basal forebrain nuclei and the midbrain pontine nuclei (100,00 cells) -- these are cholinergic neurons

action potential propagation along axon

Na+ flows into axon (makes location in axon more +) → Na+ drifts away from location and depolarizes area → adjacent Na+ channels open and Na+ rushes in! Like wave at sporting event

Na, K, Cl, Ca

major ions for neural function

gap junction

mechanical, electrically conductive link between two neighboring neurons that forms at a narrow gap between pre and post synaptic neurons clusters of proteins form channels in membranes of 2 adjacent cells allows ions/ATP/glucose to pass from one cell to the next 'direct' contact

paralytic shellfish poisoning

medical condition from STX poisoning. Symptoms: numbness, muscle weakness, paralysis, death (respiratory paralysis)... Treatment= artificial respiration BIG problem for whales and marine animals Highly hydrophilic-- does not cross BBB

acetate and choline

molecular precursors to ACh only nerve cells that use ACh as a NT have the capacity to make ACh from these precursors

batrachotoxins (BTX)

molecules that interacts with channel proteins and prevent channels from closing. If Na+ channel open all the time, Na+ flows continuously⇒ no action potential! (nerve signals don't work= muscle weakness and paralysis) Secreted from skin in certain tropical frogs-- Phyllobates terribilis (by ingestion of insects, maybe) and New Guinea pitohui bird

diffusion

particles move apart and distribute uniformly over whatever volume of fluid is available high to low concentration ("down gradient") process behind a semipermeable membrane (some solutions ___ through)

ionotropic ACh receptors

positive Na ion channels depolarize/excitatory mediate communication between nerves and skeletal muscles this NT acts on both ____ and GPCR

paracelsus

16th century Swiss Physician and alchemist; taught that all substances are poison and whether something acts as a poison or a medicine depends on the dose! Everything is a poison! Even water!

ionotrophic and GPCRs

2 kinds of NT receptors 1: glutamate, GABA, and acetylcholine (and glycine) ... also 5HT3 for Serotonin 2: all other NT receptors -- there are ones that interact with glutamate, GABA, and ACh

serotonin

5-hydroxytryptamine/ 5HT Amino acid tryptophan→ amino acid decarboxylase→____ found to have effects on constriction and dilation of blood vessels in 1940s produced in raphe nuclei affects mood/appetite/sleep

nicotinic AChRs

AChR activated by binding ____. This AChR is blocked (antagonized) by the molecule tubocurarine (plant extract used for arrow-tip poison by native hunters in Amazon jungle). This is the neurotransmitter receptor at the neuromuscular junction, and is also present in the brain. Produces muscle paralysis Ionotropic receptor.

muscarinic AChRs

AChR activated by the molecule muscarine, from mushrooms (Amanita muscarine). This AChR is blocked/antagonized by atropine. This is found in the parasympathetic neural connections with target organs as well as in the brain Metabotropic receptor

agonist

Activates a neurotransmitter receptor when it binds to it. Like the wrong key opening a lock. ____ drug mimics neurotransmitter to fit its receptor.

multiple schlerosis

Autoimmune damage to myelin → nerve conduction impaired (motor or sensory); variable symptoms--blurred vision, numbness, pains; unknown cause

antagonist

Binds to a neurotransmitter molecule and blocks action of the neurotransmitter at the receptor. Like blocking the right key from opening the lock.

blood-brain barrier

Blood vessels are constructed within the Central NS (brain and spinal cord) to regulate the passage of material from the blood into the brain (visa versa). Blood vessel walls have no gaps, pores, or holes between cells (gaps allow exchange of molecules between tissue and blood) cross by transporter proteins (glucose and some amino acids) or by dissolving through blood vessel cell walls --- molecules that do this must be highly hydrophobic/lipophilic (oxygen and drugs)

local anesthetics

Chemicals that produce a loss of sensation only in the region of the body near where they have been applied (altering Na+ channels). When the chemical drifts around, enters the bloodstream, and reaches other parts of the body, its concentration is too low to have any effects.

epilepsy

Condition of recurrent seizures (runaway overexcitation) Treatment: reduce excitation or increase inhibition! They interfere with voltagegated sodium, potassium, and calcium channels; facilitate the inhibitory action of GABA; and reduce the excitatory action of glutamate You want to blunt excitability enough so that seizures are prevented, but not so much that the normal functioning of the brain is impaired.

depolarization

Decrease in separation of charge across a cell membrane (more positive) opening Na or Ca channels has this effect on the cell charge less polarized, closer to 0

parasympathetic NS

Decreases heart rate, constricts lung airways, constricts pupils of eyes, stimulates salivation, stimulates bladder to void, stimulates intestinal motility Rest and Digest for upper/middle body, neural fibers connect with CNS via cranial nerves 3, 7, 10 lower body connect via lower end of spinal cord these fibers then connect with cluster of neurons called ____ ganglia

Acetylcholinesterase (AChE)

Enzyme responsible for ACh→ acetate and choline its release at axon terminals. (ACh removed from synaptic cleft by rapid enzyme degradation)

Choline acetyltransferase

Enzyme that catalyzes the synthesis of acetate and choline→ ACh. The gene coding for this enzyme is expressed only in cholinergic neurons (neurons w/ ACh as neurotrans)

cocaine

First local anesthetic to be appreciated in modern medicine. Molecules bind to voltage-gated Na+ channels, alter generation of action potentials (do not block completely) ⇒ reduction of signals from neurons sending sensory info into brain

metabotropic receptor

GPCR affect chemistry inside the cell binding of NT to receptor doesn't directly open ion channel... variety of effects: ion channel opens/closes, enzymes activate/deactivate, gene transcription turns on/off, etc. take longer but effects are more prolonged/amplified/variation

oligodendrocytes

Glial cells in CNS (brain); makes up myelin

schwann cells

Glial cells in PNS (body); makes up myelin

hyperpolarization

Greater separation of charge across a cell membrane (more negative) -- more polarized further from 0 opening the K or Cl channels has this effect on the cell membrane

LD 50

Lethal dose; amount of substance that kills 50% of test sample.

TTX Resistance

May result from tiny mutations that change only a single amino acid in the voltage-gated Na+ channel. This happens in animals harboring TTX. Ex. some garter snake species eat newts containing TTX typically a tweak in NA channels so TTX cannot bind --> resistance of toxin

pharmakon

Medicine and poison at the same time

saxitotoxin (STX)

Molecule that also blocks Na+ channels in a similar way to TTX and similarly interferes w NS function. Found in several species of dinoflagellates (plankton)

dopamine

NT for pleasure/reward

acetylcholine

NT of parasympathetic NS and first molecule recognized as a NT

norepinephrine

NT released for stress noradrenaline

GPCR signalling

Neurotransmitter binds to metabotropic receptors → receptor shift shape and make it able to bind another protein called a G-protein → G-protein activated→ G-protein interacts w/ effector enzyme (adenylate cyclase) → intracellular cAMP concentration changes→ cAMP interact w proteins, altering enzymatic activities (some are protein kinase) → channels open/close, genes turned on/off, etc.

saltatory conduction

Propagation of action potential from one node to the next. Neural signal travels much faster down the axon. Like express bus v. normal slow bus

ion channels

Proteins (polypeptides of hundreds of amino acids folded up) in the phospholipid bilayer membrane that open and close, allowing specific ions to pass through & cross the membrane when the channels are open

voltage gated ion channels

Sodium (Na+) and Potassium (K+) channels Pumps open (-50 mV) and close depending on membrane voltage If -50 mV voltage of positive charge, Na+ channel opens and Na+ flows into cell (making cell and voltage more positive). Once voltage reaches 30+ mV, Na+ channel closes and lets no more Na+ into cell By 30+ mV, K+ channel opens and K+ flows out of cell, causing membrane voltage to be less positive. Enough K+ moves out of cell to return cell to resting potential -65 mV. K+ channel closes The Na/K pumps then turn on and reestablish the inside/outside concentration differences

nodes of ranvier

Small gaps in the myelin, all of the voltage-gated channel proteins and Na/K pump proteins are jammed together at the the guy who discovered these discovered that myelin is not continuous along axon

synaptic vesicle

Small spheres formed of lipid bilayer membrane, each filled with several thousand neurotransmitter molecules. They bind to specific proteins in the boundary membrane of the axon terminal and then the neurotransmitters are released into the synaptic cleft.

Tetrodotoxin (TTX)

Sticks to and Blocks voltage-gated sodium channels so that sodium can't get into the cell when the channel opens. This prevents the neurons from sending signals ⇒ numbness (b/c signals from sensory neurons don't reach brain!) Muscle weakness, difficulty moving, paralysis (respiratory/ difficulty breathing) never enters brain bc not hydrophobic enough, cannot pass through BBB occurs in pufferfish!!!!

Parasympathomimetic

Stimulating effects on the parasympathetic nervous system (same effect as Sympatholytic)

Alan Hodgkin (1914-1998) & Andrew Huxley (1917-2012)

Studied the axons of squids and recorded action potentials from inside a nerve fiber. Discovered how direct measurement of voltage changes across an axon membrane during action potential. when neural signal travels along axon= voltage-gated ion channels

atropine

The deadly nightshade plant. It is a parasympatholytic and will therefore slow intestinal motility. Anticholinergic effects means it blocks parasympathetic neural activity. This makes it a useful medicine to treat diarrhea, spastic colon, and other gastrointestinal problems. Cross BBB= psychoactive effects are dreaming and hallucinations, disorientation and confusion, lack of memory

axon hillock

The place where the axon emerges from the soma of the cell. There is a high density of voltage-gated sodium and potassium channels here. This is where the action potential is initiated

seizure

Too much excitation and not enough inhibition may set off a kind of explosive chain reaction called excitation (runaway neural activity) 1% of US pop.= 3 mil Results: sudden change of sensory perception, emotional or cognitive changes, involuntary muscle movements, Amnesia/memory loss,

parasympathetic

____ NS activates circular sphincter muscles to pull iris closed in the process of eye dilation

sympathetic

_____ NS activate radial muscles to pull iris back and dilate eyes when your eyes dilate

action potential

When a signal passes along a nerve cell's axon, a striking change in membrane voltage occurs, this is ________. This is the result of electrically charged particles moving across the membrane occurs when there is a large enough depolarization (all one charge) of the cell. Membrane potential goes from resting potential of 65 mV to +30 mV and then returns back to resting potential. This all occurs in 4 milliseconds.

ATP

adenine, ribose sugar (carbon-oxygen ring), 3 phosphate groups linked by covalent phosphorus- oxygen bonds

sedative-hypnotic drug

alcohol, barbiturates, benzodiazepines, general anesthetics, other pharmaceuticals

Sympatholytic

any drug that Decrease the effects of the sympathetic nervous system on target organs

Sympathomimetic

any drug that has Stimulating effects on the sympathetic nervous system

SNARE complex

attachment proteins between vesicles and other specific proteins in boundary membrane of axon terminal poise vesicles to fuse with boundary membrane of axon

PNS

autonomic NS, neuromuscular NS, sensory NS, enteric NS connections from spinal cord to muscles throughout the body

CNS

brain and spinal cord

basal forebrain nuclei & midbrain pontine nuclei

brain regions that produce ACh

dendritic spine

bulge on a dendrite that increases surface area available for receiving signals

neuromuscular junction

chemical synapse formed by contact between a motor neuron and muscle fiber

cranial nerves

connections between CNS/PNS enter and exit at several points in the brainstem Olfactory (1), Optic(site)(2), auditory-vestibular (inner ear/balance)(8), vagus (brain to lungs and heart)(10)

phosphorus-oxygen bond

contains lots of energy that is released when they are broken by enzymatic reactions in a cell. That energy is then available to other cellular processes. ATP is the primary currency for powering cellular processes

Otto Loewi

discovered concept of chemical neurotransmission in 1920 Through frog heart experiment (puts fluid heart is in when slows down into other container with other heart→ 2nd heart slows down), resolved that a soluble chemical substance MUST be released when vagus nerve is stimulated (chemical substance mediated signal nerve→ heart) => Chemical neurotransmission!!!

ventral tegmentum & substantia nigra (midbrain)

dopaminergic brainstem nuclei

peptide NT

endorphins Composed of polypeptides. These are the opioids, collectively called the endorphins.

25, 60

energy consumption by human brain ___% per day , ___% of this goes to the NA/K Pump

glutamic acid decarboxylase

enzyme that turns glutamic acid (neutral glutamate) into GABA all cells contain glutamic acid (1 of 20 building block amino acids)

EPSP

excitatory postsynaptic potential if there is enough, there will be a depolarization in the cell and an action potential will initiate

myelin

formed when particular kinds of glial cells develop large, flattened bodies and wrap around and around the axon largely composed of layers of lipid bilayer membrane, 70% is lipid, 20% cholesterol (structural integrity and fluidity of membranes), and the rest is protein (link the layers together so it doesn't unravel)

IPSP

inhibitory postsynaptic potential if more of this, there will be hyperpolarization in the cell produced by Cl flowing into the cell or K flowing out of the cell

symbiosis

interaction between two different organisms living in close physical association, typically to the advantage of both.

K

ion concentration on the inside, these elements have a higher concentration on the inside

Na, Cl, Ca

ion concentration on the outside, these elements have a higher concentration on the outside

na/k pump

ion-transporter protein found in all neurons 3 ___ 2 ____ in one pump

connexon

made up of component proteins, pairs join to form an electrical synapse

GABA

major inhibitory NT in the brain its receptors are ionotrophic receptor Cl channels hyperpolarizes the cell -- moves membrane potential further away from the triggering of opening v-gated Na channels

glutamate (aka glutamic acid)

most abundant NT in the human brain primary excitatory NT most neurons have receptors for this NT on their surface these receptors are ionotrophic with Ca and Na channels thus depolarize the resting potential and induce action potential

chemical synapse

most common 'synapse', more complex/specialized allows for feedback/regulation opportunities

sympathetic ganglia

neural fibers of the sympathetic NS emerge from the spinal cord and form connections with these clusters of nerve cells they're just outside the spinal cord and along its length

locus coeruleus

noradrenergic cells in pons 100,000 cells epinephrine also produced here (very few though)

excitotoxicity

overexcitation of neurons by glutamate= toxic!! Can cause death!! overexcitation= many ionotropic glutamate receptors allow large amounts of Ca++ into cell ⇒ normal processes inhibited

sympathetic NS

part of autonomic NS "fight or flight" Increases heart rate, dilates lung airways, dilates pupils, inhibits salivation, inhibits bladder from voiding, decreases intestinal motility

monoamine NT

psychostimulant activity dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline) made form essential amino acid - phenylalanine

autonomic NS

regulates various body organs and internal functions like heart rate, bp, respiration, digestion mostly outside our awareness

-65 mV

resting membrane potential (inside is more negative than the outside) The voltage across the neuronal membrane will be used to power the transmission of a signal along the cell's axon

pharmacology

scientific study of drugs: origin, compositions, and effects on the body

raphe nuclei

serotonergic neurons on brainstem 200,000 cells

norepinephrine

sympathetic nervous system NT GPCR receptor

botulinum toxin

taken into ACh presynaptic terminals, interferes w neurotrans release, reduces effectiveness of ACh at neuromuscular junction! ⇒ paralysis of muscles locally (cholinergic chemical synapse)

caffeine, ethyl alcohol (ethanol), nicotine, areca nut, cannabis

top 5 psychoactive drugs in order

iontrophic receptor

transmitter binds to one receptor protein and opens ion channel does one thing VERY QUICKLY Neurotransmitter binds to postsynaptic receptor→ ion channel opens → specific ions flow in → membrane potential changes ⇒ rapid change in excitability!

causes of seizure

tumor, brain infection, high fever, injury to head, drugs, sleep deprivation, bright light

idiopathic seizures

type of seizure with unknown, unidentifiable cause (most often in childhood)

ion pump

uses energy to move specific ions from one side of the membrane to the other

Hyponatremia

when Na in body is abnormally low; H2O abnormally high

end of axon

where to calcium channels open Calcium channel opens, Ca++ flows into cell→ Ca++ binds to SNARE complex→ fusion of vesicular membrane with axon terminal→ neurotransmitter vesicles release into synaptic cleft

synaptic cleft

~20 nm separates presynaptic axon terminal and postsynaptic cell, narrow gap filled with h20 and ions NT bounced around here by thermal agitation and diffusion