Lecture 4 - Introduction to the Nervous System Flashcards
What are the four main types of cells in the brain and what are their basic function?
- Neurons - Excitable
- Microglia - Immune
- Astrocytes - provides nutrients, support, BBB
- Oligodendrocytes - myelination
Define
Excitable cells
Cells that can be electrically excited resulting in the generation and propagation of action potentials
Ex. neurons, cardiac, skeletal muscles cells, endocrine cells
Define
Non-excitable cells
Cells that are unable to generate and propagate an action potential or respond to electrical stimuli
Ex. kidney cells, adipocytes, skin cells, RBCs, microglia
Most FDA approved drugs target receptors where?
Neurons
a few in microglia and astrocytes
List the types of voltage-gated ion channels in the brain
- Sodium
- Potassium
- Calcium
List the types of ligand-gated ion channels in the brain
- Nicotinic acetylcholine receptors
- GABAA receptors
- NMDA, AMPA, and kainate types of glutamate receptors
- 5-HT3 receptors
- Gylcine receptors
What are the two other types of ion channels that can be found in the brain?
- Mechanosensitive ion channels
- Thermosensitive ion channels
What is the resting membrane potential of neurons?
-65 mV to -75 mV
What ions are in higher concentration INSIDE of neurons at resting potential?
K+
What ions are in higher in concentration OUTSIDE of neurons at resting potential?
Na+, Cl-, Ca2+
What are the basic steps in neural communication?
- Stimuli are recieved by the dendrites and cell body
- Synaptic stimuli are summed at the axon hillock where action potential is triggered if the sum of arriving signals is enough
- Action potentials are conducted to the axon terminal
- Release of neurotransmitters into the synaptic cleft
- Neurotransmitters bind to receptors in the postsynaptic cell membrane to create a new signal
Define
Action potential
The robust and quick change in membrane potential, associated with the passage of an impulse along the membrane of a neuron or muscle cell
Define
Hyperpolarization
when the membrane potential becomes more negative at a particular spot on the
neuron’s membrane
Define
Depolarization
When the membrane potential movesaway from resting potential and closer to the positive
What happens after the membrane potential depolarizes past the threshold of excitation?
Voltage-gated Na+ channels open and allow Na+ to enter the cell quickly
K+ channels open more slowly to release K+ out of the cell
At about what voltage do the Na+ channels close and K+ channels stay open?
+40 mV
What causes the refractory period in neurons?
Hyperpolarization after an overshoot of K+ ions leaving the cell
How does the cell return to resting potential?
With the assistance of Na+-K+ pumps
Where is there a buildup of + charge inside the axon and - charges outside the axon?
At the nodes of ranvier
Define
Saltatory conduction
Allows eletrical nerve signals to be propagated long distances at high rates without any degradation of signal
Common steps in Synaptic Transmission
- Neurons synthesizes neurotransmitters and stores them in vesicles
- Action potential traveling down the neuron depolarizes the presynaptic nerve ternimal
- Membrane depolarization activates voltage-dependent Ca2+channels allowing entry into the neuron
- Cytosolic Ca2+ enables vesicle fusion with the plasma membrane and releases the neurotransmitter
- Neurotransmitter binds to ionotropic receptors and metabotropic receptors
- Neurotransmitters are recycled by reuptake transporters or degraded by enzymes to terminate signal
- Enzymes such as phosphodiesterases degrade postsynaptic intracellular signalling molecules
Define
Neurotransmitters
Endogenous substances that transmit nerve impulses across synapses
What are the key neurotransmitters?
- Glutamate (excitatory)
- glycine and GABA (inhibitory)
List some of the amino acid derivatives that also modulate neuronal function
Dopamine, noepinephrine, histamine, adenosine, serotonin
Where does acetylcholine mostly function?
At the neuromuscular junction and in the parasympathetic system
Define
Ionotropic receptors
- Causes channel opening
- Causes change in membrane potential
- Acts quickly when activated
- Transmembrane, ligand-stimulated
Define
Metabotropic receptors
- Activates intracellular cascades
- Acts slowly
- Transmembrane, ligand-stimulated
What are the direct and indirect effects of GABA or glycine on ion movement?
Direct: Cl- moves into cell
Indirect: K+ moves out of cell and Ca2+ channel closes
What are the direct and indirect effects of glutamate or acetylcholine on ion movement?
Direct: Na+ and Ca2+ enter the cell
Indirect: Ca2+ enters the cell and K+ channel closes
What is the indirect effect of metabotropic receptors?
Metabotropic receptors activate a G-protein that in turn activates cyclases to generate a secondary messenger, that in turn indirectly activates or closes ion channels
Define
Autonomic nervous system
- Nerves that travel to the smooth and cardiac muscle (involuntary muscle)
- Regulate the rate at which irgans work
- Divided into the sympathetic and parasympathetic system
Define
Sympathetic Nervous System
Acute stress response
- increased heart rate, bronchodilation, and blood pressure
- decreased in activity of unrequired organs
Nerves originate from the thoracic and lumbar spinal nerves (T1-T3)
Define
Parasympathetic Nervous System
Most active during periods of rest, digestion, restoration, elimination, and reproduction
Originates from cranial nerves 3, 7, 9, 10 and sacral nerves S2-S4
Effect of sympathetic and parasympathetic stimulation
Adrenal medulla
Sympathetic: release of epinephrine
Parasympathetic: none
Effect of sympathetic and parasympathetic stimulation
Arteries
Sympathetic: vasoconstriction and vasodilation of coronary and skeletal muscle arteries
Parasympathetic: most arteries not supplied by this system
Effect of sympathetic and parasympathetic stimulation
Heart
Sympathetic: Increased heart rate, AV conduction, and contractility
Parasympathetic: Decreased heart rate, AV conduction, and slight decrease in contractility
Effect of sympathetic and parasympathetic stimulation
Intestines, GI motility, secretions
Sympathetic: Decreased function
Parasympathetic: Increased function
Effect of sympathetic and parasympathetic stimulation
Postganglionic neurotransmitter
Sympathetic: Norepinephrine released
Parasympathetic: Acetylcholine released
Effect of sympathetic and parasympathetic stimulation
Pupil of the eye
Sympathetic: Dilation (mydriasis)
Parasympathetic: Constriction (miosis)
Effect of sympathetic and parasympathetic stimulation
Lower respiratory passages
Sympathetic: Bronchodilation
Parasympathetic: Bronchoconstriction
Effect of sympathetic and parasympathetic stimulation
Urinary bladder
Sympathetic: Relaxation
Parasympathetic: Constriction
Effect of sympathetic and parasympathetic stimulation
Urinary sphincter
Sympathetic: Contraction
Parasymapthetic: Relaxation
How does the sympathetic system cause vasodilation and vasoconstriction?
Strong sympathetic tone causes vasocontriction, weak sympathetic tone causes vasodilation
Autonomic ganglion
-Made of ganglion nerves and the collection of synapses between pre- and post- nerve fibers
- Acetylcholine released in parasympathetic nerves
Preganglionic nerve fiber
- Nerves that emerge from the central nervous system leading to the ganglion
- Acetylchoine released in sympathetic nerves
Postganglionic nerve fiber
- Nerves that emerge from the ganglion to the internal organ
- Norepinephrine released in sympathetic nerves
- Acetylcholine released in parasympathetic nerves
Adrenergic Receptors
Alpha 1 - Signaling mediators
Gq, Gi, G0
Adrenergic Receptors
Alpha 1 - Tissues and effects
- Vascular smooth muscle - contraction
- Genitourinary smooth muscle - contraction
- Intestinal smooth muscle - relaxation
- Heart - increased inotropy (contraction strength) and excitability
- Liver - gluconeogenesis, glycogenolysis
Adrenergic Receptors
Alpha 2 - Signaling mediators
Gi, G0
Adrenergic Receptors
Alpha 2 - Tissues and effects
- Nerve - decreased norepinephrine release
Adrenergic Receptors
Signaling mediator for Beta-1, Beta-2, and Beta-3
Gs
Adrenergic Receptors
Beta 1 - Tissues and Effects
- Heart - increased inotropy and chronotropy (heart rate)
- Heart - increased AV node conduction velocity
- Renal juxtaglomular cells - renin seretion
Adrenergic Receptors
Beta 2 - Tissues and effects
- Smooth muscle - relaxation, glycogenolysis, gluconeogenesis, k+ uptake
Adrenergic Receptors
Beta 3 - Tissues and effects
- Adipose - lipolysis
Cholinergic Receptors
Muscarinic receptors
- GPCR, metabotropic
- located on cell membranes of visceral organs, glands, and the brain
- M1, M3, and M5 are excitatory
- M2 and M4 are inhibitory
Cholinergic Receptors
M1 - location and response
- Autonomic ganglia - late excitatory postsynaptic potential
- CNS - complex: arousal, attention, and analgesia
PLC activation –> increased DAG and IP3 –> increased Ca2+ and PKC
Cholinergic Receptors
M2 - locations and responses
- Heart: SA node - slowed spontaneous depolarization/hyperpolerization
- Heart: AV node - decreased conduction velocity
- Heart: Atrium - decreased refractory period and contractile force
- Hear: Ventricle - slight decrease in contractility
Inhibition of AC and increased K+ channel opening
Cholinergic Receptors
M4 and M5 - location
CNS
M4 same as M2 and M5 same as M1
Cholinergic Receptors
M3 - location and response
- Smooth muscle - contraction
Same mechanism as M1
Cholinergic Receptors
Nicotinic receptors
- Ionotropic
- all excitatory
Cholinergic Receptors
Nicotinic Nerve (Nn) recpetor - location and response
- Autonomic ganglia - depolarization and firing of postganglionic neuron
- Adrenal medulla - Secretion of catecholamines
- CNS - Complex: arousal, attention, analgesia
Opening of Na+/K+ channels
Cholinergic Receptors
Nicotinic Muscle (Nm) receptors - Location and response
- Skeletal muscle at neuromuscular junction - end-plate depolarization, skeletal muscle contraction
Opening of Na+/K+ channels
