Synaptic Transmission Flashcards
Membrane potential at rest?
- polarized -70mV
- positive on outside
- negative on inside
Depolarization?
- Na flows inside and charges become reversed
- positive charge on inside
What do local anesthetics do?
- block entrance of Na into cell, causing it be inactive
- sensory: pain transmission blocked
- motor: muscle paralyzed
Repolarization?
- K flows out of the cell and charges return
- positive outside
- negative inside
Absolute refractory period?
- membrane is completely inactive
- another stimulus has no effect
Relative refractory period?
- membrane is excitable
- needs stimulus above threshold
Na-K pumps?
- actively pump Na out of the cell, K into the cell
- against concentration gradients
Single cell gradation?
- no gradation
- all or none response
Nerve conduction gradation?
- each individual axon has different threshold
- full nerve has graded response
- AP height can increase as stimulus strength increases
- limit reached when threshold of all axons making nerve have been reached
- potential for increased nerve conductance
Types of ion channels?
- Non gated: passive, always open
- Gated: active, always open
- independent from each other
- open channels are activated= increased conductance
- closed channels are inactive= decreased conductance - Voltage gated:
- voltage sensitive
- operation related to membrane potential inside cell
- shifts open
- Na, K, Ca
- Ca and beta blockers can slow HR - Chemical gated:
- ligand gated or receptor gated
- operation dependent upon interaction of biological chemical (NTs) with receptors
- ligands: ACh or GABA
- Chloride
Channelopathies?
- diseases caused by genetic defects in ion channels
- some types of arrhythmias and convulsive disorders (epilepsy)
Duration of action potential?
- 15 msec
- all or none
Saltatory conduction?
- signal jumps from small unmyelinated regions called Nodes of Ranvier to another node
- pathway is myelinated
- AP propagates
Non propagated action potential?
- nonmyelinated
- no nodes of ranvier
- signal is slow and weakly transferred as it moves away from origin
- occur at junction of nerve terminal and dendrite
- Multiple Sclerosis (clinical demyelination)
Autoreceptors?
- function as part of negative feedback loop
- when activated, decreases amount of NT released into synapse
- prevents over stimulation of post synaptic membrane
- homeostasis mechanism
- excessive stimulation of post synaptic membrane causes down regulation and physical dependence
What type of effect is a chloride channel?
-inhibitory
Spacial summation?
- multiple presynaptic terminals located at different release NT on one postsynaptic membrane
- release at exact same time
- each change of 1mV can be summated to 15 mV, cumulative effect
Temporal summation?
-rapid repetitive stimulation from one presynaptic terminal can release sufficient NT to trigger post synaptic potential
Monosynaptic vs polysynaptic transmission?
- Mono
- signal across just one synapse
- very rapid (throw football from point A to B)
- reflex responses - Poly
- transmit signals across multiple synapses
- takes much longer (students passing football along)
- can be impaired
What you need in order to classify a chemical as a neurotransmitter?
- must be in nerve terminal
- has capacity to synthesize substances and accumulate substance
- capacity to store substance
- released upon nerve stimulation
- causes change at postsynaptic membrane
- process to inactive substance
- catabolic enzymes
- reuptake mechanism
How many directions can a synapse travel?
- one direction
- presynaptic to postsynaptic
Duration of postsynaptic potentials vs time NT can act on postsynaptic membrane?
- PSP: 15 msec
- NT: hundreds of msec, secs, mins, hours
Amount of voltage needed to change cell activity on postsynaptic membrane?
15-20 mV
Steps of synaptic transmission?
- Synthesis of NT
- Storage of NT
- Release of NT
- Binding to postsynaptic receptors
- Effect of binding to postsynaptic receptors
- increased ionic permeability (Na, Cl, K, Ca)
- interaction with G proteins
- effect can be stimulatory or inhibitory - Termination of NT activity
- diffusion
- enzymatic inactivation
- reuptake
Cholinergic NT synthesis?
- occurs in cytoplasm
- anabolic enzyme (choline acetyl transferase) facilitates combination of choline and acetyl CoA
- Acetylcholine is formed
Where is Choline acetyltransferase synthesized?
- synthesized in perikaryon
- transported down axon to presynaptic terminal
- large quantity in cytoplasm of cholinergic terminal
Where is acetyl CoA synthesized?
synthesized by mitochondria in presynaptic terminal
Where does choline come from for NT synthesis?
-enters presynaptic terminal from extracellular fluid via active transport
Adrenergic NT synthesis in presynaptic terminal?
- Tyrosine is converted to DOPA via Tyrosine Hydroxylase (rate limiting, has fixed rate)
- DOPA is converted to Dopamine by decarboxylase
- Dopamine is converted to NE by dopamine beta hydroxylase
Why is L-DOPA given to parkinson’s patients?
-it can cross the BBB whereas DOPA cannot
Adrenergic NT synthesis in Adrenal Medulla?
- NE is converted to Epinephrine by N-methyltransferase
- stress hormone
- increases cardiac function, relaxes bronchioles, increases blood flow
- Glucocorticoids are also released in stress and increase the synthesis and release of Epi
Effect of Glucocorticoids?
Increase action of:
- Tyrosine Hydroxylase
- Dopamine beta-hydroxylase
- N-methyltransferase
- increase synthesis of Epi
Storage of Cholinergic NT?
-ACh stored presynaptic vesicles
Storage of Adrenergic NT?
-catecholamines stored in presynaptic vesicles
Resting state release of NT?
- continual release of small quantity of NT to maintain physiologic responsiveness of post synaptic cell
2.
Active state release of NT?
- Arrival of action potential at presynaptic membrane
- Activation of Na channel (voltage gated)
- Influx of Na
- Depolarization of presynaptic membrane
- Activation of voltage gated calcium channel
- Influx of Ca (vesicles fuse)
- Vesicles next to membrane fuse, NT discharged into synapse, called Exocytosis
- Amount released sufficient to change activity of target cell
- contraction of skeletal muscle
- reduced beat of heart cell
Inhibitory release of NT?
- Receptors located on presynaptic membrane are auto receptors
- Autoreceptors decrease release of NT form presynaptic membrane
- Due to decreased Calcium influx
Agonist vs Antagonist binding to postsynaptic receptors?
- Agonist
- mimic NT at its receptor - Antagonist
- bind to receptor and block it, do not activate it
NT binds to postsynaptic membrane and causes opening of voltage gated Na channels?
- Increase in Na permeability
- Na channel opens
- Na influx
- Depolarization
- Excitatory Postsynaptic Potential (EPSP)
- activation of target cell
NT binds to postsynaptic membrane and causes opening of voltage gated K channels?
- Increase in K permeability
- K channels open
- Efflux of K (loss of positive)
- Hyperpolarization (increased negativity on inside of cell)
- Inhibitory Postsynaptic Potential (IPSP)
- Inhibition of target cell (same of Cl coming in)
NT binds to postsynaptic membrane and causes opening of voltage gated Ca channels?
- Increase Ca permeability
- Ca channels open
- Influx of Ca
- Exocytosis
- EPSP in skeletal muscle contraction
- IPSP if calcium dependent K channels open (relaxation of smooth muscle in GI)
NT binds to postsynaptic membrane and causes opening of chemical gated GABA channels?
- Increases Cl permeability
- Cl channels open
- Influx of Cl
- Increased negativity inside cell (hyper polarization)
- IPSP produced
- inhibition of target cell
Na channels opened?
Excitatory
Cl or K channels opened?
Inhibitory
Diffusion to terminate NT activity?
- minor process
- small portion diffuses out of synapse
Cholinergic enzymatic inactivation of NT activity?
- Acetylcholinesterase
- principal catabolic enzyme
- hydrolyzes ACh to Choline and Acetate
- very rapid enzyme to break down ACh - Butylcholinesterase
- found only in small amounts in neurons
- more located in liver, other organs and plasma
- used to treat Alzheimers
Adrenergic enzymatic inactivation of NT activity?
- Monoamine Oxidase
- located on outer surface of mitochondria
- catabolizes (by deamination) adrenergic NTs which circulate in blood and those in nerve terminal
- MAO-A: prefers 5-HT and NE
- MAO-B: prefers Dopamine - Catechol-Oxymethyltransferase (COMT)
- primarily extracellular
- catabolizes (by methylation) NE and Epi released by nerve terminals and Adrenal Medulla
Reuptake of NT to inhibit activity?
- Adrenergic: major process for inactivation of NT
2. Cholinergic: does not exist
Factors affecting activity of CNS?
- Reduction of synaptic transmission
- Hypoxia
- Changes in blood pH
- Drugs
How synaptic transmission is reduced?
- Exhaustion of NT supply
- released faster than it can be replenished
- synaptic transmission fatigue - Development of IPSP
- rapid firing leads to Ca buildup
- K channels open
- K efflux, hyper polarization - Inactivation of Postsynaptic receptors
Hypoxia to reduce synaptic transmission?
- CNS need continual supply of O2
- disruption in circulation for 3-5 seconds will produce unconsciousness
Changes in blood pH to reduce synaptic transmission?
- normal pH = 7.4
1. Acidic pH < 7.0 - coma produced
2. Alkaline pH > 7.8 - CNS activated, convulsions
- breathe rapidly, CO2 will decrease and pH increases
- dangerous for person with epilepsy
Drugs to increase or decrease synaptic transmission?
- stimulate NT action by binding to and activating receptor
- amphetamine similar to Epi - block receptor and inactivate it
GABA-A effect?
- decreases CNS activity
- Benzos
- non benzos
Melatonin effect?
- decreases CNS activity
- Ramelteon (Rozerem)
Histamine H1 effect?
- increases CNS activity
- antagonist: Doxepin (Sinequan)
Orexin effect?
- increases CNS activity
- Narcolepsy: orexin deficient
- neuroprotective effect in alzheimers
- decreased Orexin receptors in alzheimers patients
