What is the RMP of a neuron?
What type of receptor is at the cell body and dendrite of a neuron?
(Acth) ligand gated Na+ channels
4 factors contributing to RMP?
- 1. K+ leak channels
- 2. Na+/K+ Pump
- 3. Nucleic Acids (Negative - Phosphodiester)
- 4. Cytosolic Proteins (Typically Negative)
What happens at +30 mV (AP Peak)
- Voltage Gated Na+ Channels Inactivate
- Voltage Gated K+ Channels Open (K+ Leaves Cell)
What happens at -60mV (Threshold)?
Voltage Gated Na Channels open (Na+ Enters Cell)
- Unipolar Neuron
- get a graded potential (local potential)
- causes voltage gated channels to open
- generates an action potential
- 2 cells
- Receptor cell with ligand or mechanically gated channels has graded potential (could be AP as well)
- Receptor cell releases NT onto unipolar or bipolar neuron generates an action potential sent down the nerve.
- Example: Hair cells in the ear
- RMP of pacemaker heart cells = -50mv
- Spontanteously depolarize in Sinoatrial (SA) Node.
- Called Pacemaker potential or prepotential
Leak ions and cause cyclic firing.
Need to be specific: presynaptic or postsynaptic cell?
Ligand vs. Voltage Gated Channels and Potentials
- Ligand Gated Channels cause Graded/Local Potentials
- Voltage Gated Channels Cause Action Potentials
What ions can cause Depolarization?
- Sodium Entering cell
- Calcium Entering cell
What ions cause Hyperpolarization
- Chloride Entering cell
- Potassium Leaving cell
Graded Potentials Amplitude or Frequency Modulated?
Where do graded potentials occur?
- At Dendrites and cell bodies.
- Ligand gated channels.
Are action potentials regulated by Amplitude or Frequency?
- All or nothing
- Generated at the initial segment of an axon
- new AP formed at every node of Ranvier
Is Capacitance high at the Nodes of Ranvier?
and low at myelinated internodes.
Define Ion Flux?
Movement of ions down their concentration gradient
NT released is Glutamate and causes post synaptic channel to get excited.
NT released is GABA (Gamma Amino Butyric Acid) and causes post synaptic Chlorine Channels to open (hyperpolarize / inhibit cell).
Spike Initiation Zone
Axon Hillock + Initial Segment of the axon
Last portion of the cell body featuring very low threshold voltage gated sodium channels.
Note: there are voltage gated sodium channels that open at -60mv at initial segment of the axon. This is where the AP spike occurs.
- Excitatory Post Synaptic Potential
- Encourage Firing of AP
- (Glutamate mediated)
- Inhibitory Post Synaptic Potential
- Inhibit Firing of AP
- (GABA mediated)
- Summing over time
- 3 rapid fires in succession may cause AP
- Summing over space
- 3 fires at same time in close proximity may cause AP
Another name for Cell body?
Voltage Gated Sodium Channel States
1. Closed = -70mv (RMP)
- 2. Open = -60mv (Threshold)
- 3. Inactivated = +30mv (Peak)
- back to closed
Voltage Gated Potassium Channel States
- 1. Closed = -90mv (Hyperpolarization)
- 2. Open = +30mv (Peak)
- Used to inhibit voltage gated sodium channels
- used in Labs
- Inhibits voltage gated sodium channel
- Can be used as local anesthetic
- Numbs pain by blocking Action potentials on free nerve endings by inhibiting voltage gated Na Channels
- Used for ventricular tachycardia (Fast Heart Rate)
- Slows rate at which ventricles depolarize
- Takes place on myelinated axon.
- 100 m/s
- Takes place on unmyelinated axon
- 1 m/s
2 ways to speed up ion flow in axoplasma?
- 1. increase diameter of axon
- 2. Increase myelination
- 3. decrease capacictance
Rates of A, B, C Fibers?
- A = Saltatory 100 m/s (Myelinated and larger diameter)
- B = ~50 m/s
- C = continuous 1 m/s
What Ion leaks out of the membrane in a myelination disorder?
Potassium (K). due to K leak channels.
Note: It's not sodium. It's concentration gradient wants to move sodium into cell not out.
Axon synapsing on a cell body?
Axon synapsing on a dendrite
Ligand gated ion channel
Ligand binds to receptor and initiates G protein coupled response.
Where are cholinergic synapses found?
Brain and Neuromuscular Junction (NMJ)
Two types of cholingeric receptors?
- 1. Nicotinic
- 2. Muscarinic
- * Acth binds to both
- * Acth binds to all cholingeric receptors
Properties of Cholinergic receptors?
- Excitatory or Inhibitory
- Bind Acth
- Two types: nicotinic & muscarinic
What NT do Postganglionic Sympathetic Nerves release?
What NT do Postganglionic Parasympathetic Nerves release?
What enyzme breaks down cAMP?
Cyclic AMP Phosphodiesterase
What's a prepotential?
- aka Pacemaker Potential
- Gradual change in the electrical charge at the inner surface of the cell membrane. When the charge reaches a certain value (i.e., threshold potential) there is a rapid influx of Calcium ions that leads to a heart beat.
Effect of Vagus nerve on Heart?
- 1. drips Ach on M2 (muscarinic) receptor
- 2. M2 receptor activates Gi (inhibitory g protein)3. Gi inhibits adenylyl cyclase which converts ATP to cAMP.
- 4. cAMP levels drop because they are being degraded by Cyclic AMP Phosphodiesterase
- 5. decrease in cAMP leads to decrease in SA Node Prepotential frequency (chronotropy / heart rate), and dromotropy decreases (conduction speed of action potentials through cardiac conduction system)
What is Phosphorylation?
Phosphorylation is the addition of a phosphate (PO43-) group to a protein or other organic molecule
What is Phosphorolysis?
Phosphorolysis is the cleavage of a compound in which inorganic phosphate is the attacking group. It is analogous to hydrolysis.
What is a Kinase?
a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation
What is Chronotropy?
Rate at which prepotentials form.
What is Dromotropy?
Conduction speed of action potentials through cardiac conduction system
Heart Rate on Table?
Heart Rate in body?
- On Table= 110 beats / min
- In Body = ~70 beats / min
What is Vagal Brake?
The vagus acts as a restraint, or brake, limiting heart rate by dripping on ACh on cardiac muscle receptors.
What causes heart rate to increase when exercising?
- 1. Withdrawal of parasympathetic tone.
- 2. sympathetic nervous system kicking in.
What does Atropine do?
Increases Heart Rate by blocking ACh binding on M2 receptor and consequently removing the parasympathetic tone.
What are catecholamines?
3 properties of Adrenergic Synpases?
- 1. Abundant in CNS and ANS
- 2. Bind catecholamines (norepi, epi, dopamine)
- 3. Excitatory or Inhibitory
Where does Norepinephrine come from?
Post ganglionic sympathetic nerves
Where does Epinephrine come from?
Adrenal Gland (Adrenal medulla)
What is the pathway to make Epinephrine?
Tyrosine -> L-Dopa -> Dopamine -> Norepi -> Epi
What is PNMT?
- An enzyme that converts Norepinephrine to Epinephrine in Adrenal Medulla.
- (Adrenal medulla makes 75% epi, 25% norepi)
What is Parkinson's Disease?
Not enough dopanergic synapses in basal ganglia of brain (neurons are gone)
Dopamine can't pass BBB so treated with L-Dopa (which can pass the BBB)
What does Protein Kinase A (PKA) do?
- PKA is activated by cAMP
- Phosphorylates enzymes and Activates them.
What are HCN Channels?
- Heterocyclic nucleotide Channels.
- cAMP (a cyclic nucleotide) internally binds to ligand gated channel and opens it (occurs on P-face)
- Contain NT GABA
- Always Inhibitory
- GABA binds to Ligand gated Chloride Channels
- Causes cell to become hyperpolarized (inhibited)
- Most abundant inhibitory NT in Brain
What do benzodiazepines do?
Keep Ligand Gated Chloride channels open even if GABA not present.
example: Diazepam (Valium) used for Anxiety and Sedation.
- Most abundant excitatory NT in Brain
- Contain NT Glutamate (an Amino Acid)
- Typically Excitatory
- Binds to 2 receptor types: AMPA and NMDA
AMPA receptor Properties
- Ligand Gated Na+ Channel
- Binds: 2 molecules of Glutamate
- Causes local depolarization of Cell
Name 2 major 2nd Messengers?
- Calcium (calcium calmodulin complex)
NMDA receptor properties
- Ligand and Voltage Gated Ca2+ channel
- Binds 2 molecules of Glutamate
- Ejects a Mg2+ ion from Channel once local depolarization occurs (due to AMPA receptor)
- Allows Ca2+ to enter cell
- Excitatory effects
What does Ketamine do?
- Ketamine blocks NMDA receptors
- Inhibits Post synaptic Nerve
- Used to induce anesthesia
Ways to stop Nerve signal
- 1. Stop firing the presynaptic neuron
- 2. binding event of ligand NT is brief (1 ms)
- 3. some NT diffuses out of synaptic cleft
- 4. Presynaptic knob reabsorbs (amino acids & catecholamines) and degrades in the cell (NOT IN CLEFT)
- 5. AChE degrades ACh in Synaptic cleft
What is Monoamine oxidase (MAO)?
Enzyme that degrades catecholamines (norepi, epi, dopamine) in the presynaptic knob.
* Some antidepressents can block this leading to hyper excited neurons.
what do Selective Serotonin Reuptake Inhibitors (SSRI) do?
Prevent reuptake of serotonin by presynaptic cell so it is not degraded.
Properties of Gs metabotropic receptor?
- NT: Norepi
- Recepetor: adrengeric
- G-Protein: Gs
- Effector Protein: activate Adenylyl cyclase
- Second Msg: increase cAMP
- Later effectors: Protein Kinase ATarget Action: Increase Protein Phosphorlyation
Properties of Gi metabotropic receptor?
- NT: Dopamine
- Recepetor: Dopamine D2
- G-Protein: Gi
- Effector Protein: Inhibit Adenylyl cyclase
- Second Msg: decrease cAMP
- Later effectors: decrease Protein Kinase A
- Target Action: Decrease Protein Phosphorlyation
Properties of Gq metabotropic receptor
- NT: Glutamate
- Receptor: mGluR
- G-Protein: Gq
- Effector Protein: Phospholipase C
- Second Msg: Diacylglycerol (DAG) & IP3DAG activates PKC, IP3 causes Calcium release from Smooth ER or go to membrane and cause Ca to enter cell.
- Later effectors: Protein Kinase C & Ca2+ ReleaseTarget Action: Increase protein phosphorlaytion and activate calcium-binding proteins.
Cerebellum is involved in?
- Coordination of skeletal muscle
- Receives sensory info from muscle
- Tells cerebral cortex what's going on in muscle
- Cerebral cortex tells Cerebellum what it wants to do
Basal Nuclei are involved with?
Planning and initiating movement
Parkinson's disease occurs here due to down regulation of dopaminergic synapses in basal ganglia. Can't initiate muscle movement.
* aggregation of nerve cell bodies in White Matter
Responsibility of Dorsolateral region of vental horn?
Innervate extremity muscles (arms, legs, appendages)
Responsibility of Ventromedial region of vental horn?
Innervate axial muscles (muscles of torso, neck)
Definition of Motor Unit
One alpha motor neuron and all the muscle fibers it innervates.
Definition Muscle Spindle?
- Aka Stretch Receptors
- Buried within the muscle
- Fusiform shaped
- Each muscle has many spindles
- Have both Afferent and Efferent nerves
Parts of Neuromuscular Junction
- 1. Presynaptic Terminal
- 2. Synaptic Cleft
- 3. Postsynaptic Terminal
Intrafusal vs. Extrafusal Fibers
Intrafusal Fibers = Make up spindle
Extrafusal Fibers = Actual Skeletal muscle fibers
Two Types of Intrafusal Fibers?
- 1. Nuclear Bag Fibers
- 2. Nuclear Chain Fibers
- Bag = All nuclei bunch together like a bag(1 or 2 bag fibers per spindle)
- Chain = All nuclei in a row
Type 1A Sensory Neurons
- Bring sensory info from Bag and Chain Fibers
- Innervate Bag and Chain fibers
- sense velocity & position of muscle
Type 2 Sensory Neurons
- Bring sensory info from Chain Fibers
- innervate Chain fibers only
- sense position of muscle only
Gamma / Fusimotor neurons
innervate intrafusal muscle fibers
Alpha Gamma Co-activation
Alpha and Gamma muscle fibers work in conjunction so that the muscle spindle always stays taught and sensitive to stretch.
What is syncopy?
- The medical term for fainting
- May be caused by low heart rate or low BP