Exam 2 Neurophysiology
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Questions and Answers

What is the EEG reading that correlates with a low probability of recall ?

  • 0
  • 100
  • 60
  • < 60 (correct)

    • What is the alternative to using BIS monitoring for anesthesia?

  • Motor evoked potentials
  • Auditory evoked potentials
  • Somatosensory evoked potentials
  • Maintaining end tidal concentrations of inhalation agents at 0.7-1.3 MAC (correct)

    • What is the benefit of using BIS monitoring?

  • Increased use of inhalation agents
  • Prolonged recovery time
  • Reduced drug use and more rapid return of consciousness (correct)
  • Reduced risk of recall

    • Which of the following ionotropic receptors is associated with neuropathic pain and opioid tolerance?

    <p>NMDA receptors</p> Signup and view all the answers

    What type of receptors are Glutamate receptors?

    <p>Excitatory-Ligand--gated ion channels</p> Signup and view all the answers

    Which of the following neurotransmitters is the principle inhibitory neurotransmitter in the spinal cord?

    <p>Glycine</p> Signup and view all the answers

    What is the effect of volatile inhalation agents on non-specific nicotinic receptors?

    <p>Inhibition</p> Signup and view all the answers

    Which of the following agents allosterically increases the sensitivity of the GABA receptor to GABA?

    <p>Benzodiazepines</p> Signup and view all the answers

    What type of memory is characterized by conscious recall and recognition?

    <p>Explicit memory</p> Signup and view all the answers

    What is the purpose of using EEG interpretation and somatosensory evoked potential patterns?

    <p>To detect depth of anesthesia</p> Signup and view all the answers

    What is the benefit of using the Bispectral Index?

    <p>It combines the characteristics of various EEG waveforms</p> Signup and view all the answers

    What type of ion channels are regulated by voltage changes across the cell membrane?

    <p>Voltage-gated ion channels</p> Signup and view all the answers

    What is the result of increased circulating concentrations of ligands on receptor density?

    <p>Down regulation of receptors</p> Signup and view all the answers

    What is the site of action of local anesthetics?

    <p>Voltage-gated ion channels</p> Signup and view all the answers

    What is the effect of magnesium on the synaptic transmission process?

    <p>Antagonizes the effects of calcium and decreases release of Ach</p> Signup and view all the answers

    What triggers the fusion of vesicles to the cell membrane and exocytosis during synaptic transmission?

    <p>Influx of calcium</p> Signup and view all the answers

    Which type of channels are present in neurons, skeletal muscle, and endocrine cells?

    <p>Voltage-gated ion channels</p> Signup and view all the answers

    What is the site of transmission of an action potential from the presynaptic membrane to the postsynaptic membrane?

    <p>Synapse</p> Signup and view all the answers

    What percentage of norepinephrine is recycled through reuptake?

    <p>80%</p> Signup and view all the answers

    What is the primary metabolite of norepinephrine excreted in the urine?

    <p>Vanillylmandelic acid (VMA)</p> Signup and view all the answers

    What is the enzyme responsible for combining choline and acetyl coenzyme A to form acetylcholine?

    <p>Acetyltransferase</p> Signup and view all the answers

    Which of the following is a characteristic of the adrenergic receptor?

    <p>Presence of alpha, beta, and dopaminergic subtypes</p> Signup and view all the answers

    What is the primary effect of acetylcholinesterase on acetylcholine?

    <p>Rapidly metabolize acetylcholine</p> Signup and view all the answers

    What is a common clinical manifestation of aging and autonomic nervous system dysfunction?

    <p>Orthostatic hypotension and temperature dysregulation</p> Signup and view all the answers

    What is the effect of aging on the response to beta-adrenergic stimulation?

    <p>Blunted response</p> Signup and view all the answers

    What is the consequence of the decreased ability to adapt to stress and reduced number of adrenergic prejunctional terminals in aging?

    <p>ANS dysregulation</p> Signup and view all the answers

    What is the primary advantage of myelination in neurons?

    <p>Dramatically reducing the energy required for repolarization and increasing impulse speed</p> Signup and view all the answers

    What is the effect of hypocalcemia on sodium channels?

    <p>Inhibits the closure of sodium channels</p> Signup and view all the answers

    What is the effect of hypercalcemia on neuronal excitability?

    <p>Decreases neuronal excitability</p> Signup and view all the answers

    What is the effect of hypokalemia on skeletal muscle?

    <p>Decreases skeletal muscle strength</p> Signup and view all the answers

    What is the effect of local anesthetics on sodium channels?

    <p>Blocks sodium channels and decreases myocardial contractility</p> Signup and view all the answers

    What is the consequence of hypocalcemia on resting membrane potential?

    <p>Decreases threshold by making resting potential more positive</p> Signup and view all the answers

    What is the effect of hypokalemia on skeletal muscle?

    <p>Muscle weakness</p> Signup and view all the answers

    What is the result of hypokalemia on muscle cell membrane?

    <p>Hyperpolarization of muscle cells and decreased excitability resulting in weakness</p> Signup and view all the answers

    What is the primary cause of rapid depolarization during an action potential?

    <p>Influx of sodium ions through voltage-gated ion channels</p> Signup and view all the answers

    What is an alternate name for the parasympathetic nervous system?

    <p>Craniosacral system</p> Signup and view all the answers

    What is the alternate name for the sympathetic nervous system?

    <p>Thoracolumbar</p> Signup and view all the answers

    What is the primary neurotransmitter at the neuromuscular junction?

    <p>Acetylcholine</p> Signup and view all the answers

    What are the predominant ions in the extracellular fluid?

    <p>Sodium and chloride</p> Signup and view all the answers

    What are the primary anions in the extracellular fluid?

    <p>Chloride and bicarbonate</p> Signup and view all the answers

    What are the primary ions in the intracellular fluid?

    <p>Potassium and Magnesium</p> Signup and view all the answers

    What are the primary anions in the intracellular fluid?

    <p>Phosphate</p> Signup and view all the answers

    What happens to receptor density when there are increased circulating concentrations of ligands?

    <p>Receptor density decreases (downregulation)</p> Signup and view all the answers

    What happens to receptor density as a result of drug-induced antagonism of receptors?

    <p>It increases due to upregulation</p> Signup and view all the answers

    What is the role of glutamate in the CNS?

    <p>Major excitatory/depolarizing amino acid neurotransmitter in the CNS</p> Signup and view all the answers

    What is the primary function of GABA in the CNS?

    <p>Inhibitory neurotransmitter</p> Signup and view all the answers

    What is the main neurotransmitter at the preganglionic junction in the autonomic nervous system?

    <p>Acetylcholine</p> Signup and view all the answers

    What is the neurotransmitter at the postganglionic adrenergic synapse?

    <p>Norepinephrine</p> Signup and view all the answers

    What type of receptor is the target for propofol, etomidate, and thiopental?

    <p>GABA</p> Signup and view all the answers

    How do benzodiazepines work?

    <p>By allosterically increasing the sensitivity of the GABA to GABA</p> Signup and view all the answers

    What type of nerve fibers are associated with preganglionic fibers?

    <p>B fibers</p> Signup and view all the answers

    What type of nerve fibers are the largest?

    <p>A-alpha</p> Signup and view all the answers

    What is the relationship between nerve fiber size and conduction velocity?

    <p>Larger nerve fibers have faster conduction velocities</p> Signup and view all the answers

    What is the primary function of A-alpha nerve fibers?

    <p>Innervation of skeletal muscles, proprioception</p> Signup and view all the answers

    What is the primary function of A-beta nerve fibers?

    <p>Transmission of pressure and touch</p> Signup and view all the answers

    What is the only unmyelinated nerve fiber?

    <p>C fibers</p> Signup and view all the answers

    What is the primary function of A-gamma nerve fibers?

    <p>Skeletal muscle tone</p> Signup and view all the answers

    What is the function of A-delta nerve fibers?

    <p>Transmitting fast pain, touch, and temperature</p> Signup and view all the answers

    Where are C nerve fibers found?

    <p>Postganglionic sympathetic fibers</p> Signup and view all the answers

    What is the primary function of C nerve fibers?

    <p>Transmitting slow pain, touch, temperature, and postganglionic sympathetic fibers</p> Signup and view all the answers

    How do ligand-gated receptors work?

    <p>The ligand binds to the receptor, causing a conformational change that produces an effect</p> Signup and view all the answers

    What is the role of the surface protein in a G-protein-coupled receptor?

    <p>To bind to the ligand and stimulate a conformational change in the G-protein</p> Signup and view all the answers

    What type of receptors do hormones and drugs such as catecholamines, opioids, anticholinergics, and antihistamines act through?

    <p>G protein coupled receptors</p> Signup and view all the answers

    What type of channels are the site of local anesthetic action?

    <p>Voltage-gated sodium channels</p> Signup and view all the answers

    What is the main difference between cardiac and skeletal muscle in terms of cell morphology?

    <p>Both are striated. Skeletal muscle has multiple nuclei, while cardiac muscle has a single nucleus.</p> Signup and view all the answers

    What is unique about smooth muscle cell morphology?

    <p>They have a single nucleus, are non-striated, and spindle-shaped</p> Signup and view all the answers

    What effect does pregnancy have on succinylcholine metabolism?

    <p>Decreased metabolism due to decreased butyrylcholinesterase</p> Signup and view all the answers

    Decreased metabolism of succinylcholine due to decreased butyrylcholinesterase can cause what effect on the length of neuromuscular blockade?

    <p>Longer duration of blockade</p> Signup and view all the answers

    What enzyme is responsible for metabolizing acetylcholine?

    <p>Acetylcholinesterase</p> Signup and view all the answers

    Where is acetylcholine metabolized?

    <p>Neuromuscular junction</p> Signup and view all the answers

    Where is succinylcholine metabolized?

    <p>away from the NMJ</p> Signup and view all the answers

    What is the mechanism of action of depolarizing neuromuscular blocking drugs?

    <p>Activation of nicotinic receptors, causing persistent depolarization of the muscle fiber</p> Signup and view all the answers

    What effect do depolarizing neuromuscular blocking drugs have on potassium?

    <p>They increase potassium permeability</p> Signup and view all the answers

    How many alpha sites must be bound by acetylcholine to open the receptor?

    <p>Two</p> Signup and view all the answers

    Binding of a single molecule of NDNMBD will block the AChR

    <p>True</p> Signup and view all the answers

    What action do nondepolarizing neuromuscular drugs perform at the acetylcholine receptor?

    <p>Competitive Blockade</p> Signup and view all the answers

    How do acetylcholinesterase inhibitors reverse neuromuscular blockade?

    <p>By increasing the amount of acetylcholine in the synapse by blocking reuptake by acetylcholinesterase</p> Signup and view all the answers

    How does sugammadex reverse neuromuscular blockade?

    <p>By encapsulating the steroidal NMB molecule and reversing diffusion away from NMJ</p> Signup and view all the answers

    What must also be administered with an acetylcholinesterase inhibitor?

    <p>Anticholinergic</p> Signup and view all the answers

    What are some common side effects of acetylcholinesterase inhibitors?

    <p>Bradycardia, bronchospasm, increased GI motility</p> Signup and view all the answers

    Factors that affect action of Achesterase inhibitors = degree of block, type and dose of drug, rate of clearance of NMBD, type and depth of anesthetic

    <p>True</p> Signup and view all the answers

    Acetylcholinesterase inhibitors have a ceiling effect – cannot antagonize profound or deep block

    <p>True</p> Signup and view all the answers

    What anticholinergic is used with edrophonium to reverse neuromuscular blockade?

    <p>Atropine</p> Signup and view all the answers

    What anticholinergic is used with neostigmine and pyridostigmine to reverse blockade?

    <p>Glycopyrrolate</p> Signup and view all the answers

    What precautions must be taken when administering sugammadex?

    <p>All of the above</p> Signup and view all the answers

    What is the main difference between fetal and adult acetylcholine receptors?

    <p>Fetal receptors are composed of α, β, γ, and δ subunits, while adult receptors are composed of α, β, ε, and δ subunits</p> Signup and view all the answers

    What is unique about the affinity for acetylcholine (ACh) in fetal receptors?

    <p>Higher affinity than adult receptors</p> Signup and view all the answers

    What can cause re-expression of fetal Ach receptors?

    <p>All of the above</p> Signup and view all the answers

    What effect does the increased affinity for ACh in fetal ACh receptors have on the opening/closing of the receptor?

    <p>Increased opening of the receptor</p> Signup and view all the answers

    When depolarizing NMBDs are administered in the presence of large amounts of fetal AChRs, what event can occur?

    <p>Efflux of potassium from the cell causing hyperkalemia</p> Signup and view all the answers

    How are atracurium and cis-atracurium metabolized?

    <p>Hydrolysis by esterases and Hoffman eliminatin</p> Signup and view all the answers

    What factors increase the potency of non-depolarizing neuromuscular blocking drugs?

    <p>All of the above</p> Signup and view all the answers

    What factors decrease the potency of non-depolarizing NMB drugs?

    <p>Anticonvulsants and hypercalcemia</p> Signup and view all the answers

    How does hypercalcemia counter the effects of NDNMBDs?

    <p>There is more acetylcholine in the neuromuscular junction to compete with NDNMBDs.</p> Signup and view all the answers

    Where is butyrylcholinesterase synthesized?

    <p>Liver</p> Signup and view all the answers

    What does butyrylcholinesterase metabolize?

    <p>All of the above</p> Signup and view all the answers

    What factors lower butyrylcholinesterase?

    <p>All of the above</p> Signup and view all the answers

    What is the movement of neuromuscular blocking drugs from the neuromuscular junction while repetitively binding and unbinding to post-junctional receptors called?

    <p>Buffered diffusion</p> Signup and view all the answers

    In which type of neuromuscular blocking drugs is buffered diffusion prevalent?

    <p>Long-acting</p> Signup and view all the answers

    Which of the following neuromuscular blocking drugs have a rapid onset?

    <p>A and B (Succs and Roc)</p> Signup and view all the answers

    What types of neuromuscular blockers does sugammadex reverse?

    <p>Aminosteroidal-based</p> Signup and view all the answers

    What are some examples of aminosteroidal neuromuscular blockers?

    <p>All of the above</p> Signup and view all the answers

    What is the affinity order of sugammadex for aminosteroidal NMBAs?

    <p>Rocuronium &gt; vecuronium &gt; pancuronium</p> Signup and view all the answers

    What is the major route of elimination of sugammadex?

    <p>Urinary excretion</p> Signup and view all the answers

    What is the relationship between the Dihydropyridine receptor and the Ryanodine receptor complex?

    <p>The Dihydropyridine receptor acts as a voltage sensor for EC coupling and passes the action potential along to the Ryanodine receptor which ultimately releases calcium from the sarcoplasmic reticulum</p> Signup and view all the answers

    Which neuromuscular blocking drugs have an intermediate onset and duration?

    <p>Atracurium and Cisatracurium and Vecuronium</p> Signup and view all the answers

    What makes mivacurium a poor choice as a NMB?

    <p>Its slow onset and short duration of action</p> Signup and view all the answers

    What neuromuscular blocking drug is known to cause bradycardia, especially during the second dose?

    <p>Succinylcholine</p> Signup and view all the answers

    Why is Tubocurarine a poor neuromuscular blocking drug (NMBD)?

    <p>It has a slow onset and a long duration of action</p> Signup and view all the answers

    Which of the following neuromuscular blocking drugs can cause tachycardia?

    <p>Succinylcholine and Pancuronium,</p> Signup and view all the answers

    Which neuromuscular blocking drugs cause histamine release?

    <p>Benzylisoquinolinium agents (Tubocurarine and Atracurium)</p> Signup and view all the answers

    What is the metabolic byproduct of atracurium elimination and where is it excreted?

    <p>Laudanosine, Liver</p> Signup and view all the answers

    What neuromuscular blocking drugs are metabolized by butyrylcholinesterase?

    <p>Succinylcholine and Mivacurium</p> Signup and view all the answers

    How does hypokalemia affect resting membrane potential?

    <p>It becomes more negative and thus less excitable</p> Signup and view all the answers

    What is the normal resting potential of a cell?

    <p>-70mV (-60 to -90)</p> Signup and view all the answers

    What is the normal resting potential of a skeletal muscle cell?

    <p>-90 mV</p> Signup and view all the answers

    What is the threshold potential in millivolts (mV)?

    <p>-55</p> Signup and view all the answers

    What type of receptor subtype does the NMDA receptor fall under?

    <p>Ionotropic Glutamate Receptor</p> Signup and view all the answers

    How does hypocalcemia cause tetany?

    <p>By increasing the permeability of the neuronal membrane to sodium (negative feedback loop)</p> Signup and view all the answers

    What is the primary difference between a phase I and a phase II block in neuromuscular blockade?

    <p>Phase I block is a depolarizing block, while phase II block is a non-depolarizing block</p> Signup and view all the answers

    Which cranial nerves innervate the parasympathetic nervous system?

    <p>Cranial nerves III, VII, IX, and X</p> Signup and view all the answers

    Where is norepinephrine primarily metabolized?

    <p>Liver</p> Signup and view all the answers

    What is the nature of the muscarinic receptors in the parasympathetic nervous system?

    <p>They are inhibitory and slow the heart rate</p> Signup and view all the answers

    Where do upper and lower motor neurons synapse?

    <p>Ventral horn of the spinal cord</p> Signup and view all the answers

    There are no muscarinic receptors in the sympathetic nervous system

    <p>True</p> Signup and view all the answers

    Acetylcholinesterase inhibitors have a ceiling effect and cannot reverse a deep block

    <p>True</p> Signup and view all the answers

    How many alpha subunits on the AchR does succinylcholine have to occupy to initiate blockade?

    <p>1</p> Signup and view all the answers

    What is unique about cisatracurium as compared to atracurium? (select 2)

    <p>It is more potent</p> Signup and view all the answers

    Study Notes

    Anesthesia and Consciousness

    • Values of anesthesia correlate with depth of anesthesia, with an isoelectric EEG at 0 and a wide-awake state at 100
    • May allow for reduced drug use and more rapid return of consciousness
    • An alternative is to maintain end-tidal concentrations of inhalation agents at 0.7-1.3 MAC

    Somatosensory Evoked Potentials

    • Stimulation of a peripheral nerve (wrist or ankle) with a low-voltage current
    • Monitoring transmission to the somatosensory cortex
    • Volatile inhalation agents block the response in a dose-dependent manner

    Motor Evoked Potentials

    • Requires direct (epidural) or indirect (trans-osseous) stimulation of the brain or spinal cord
    • Assesses motor pathways
    • May eliminate the necessity of an intraoperative wake-up test during spinal surgery

    Auditory Evoked Potentials

    • Arise from brainstem auditory pathways

    Norepinephrine Metabolism

    • After release, norepinephrine is recycled or metabolized
    • Reuptake (80%) or metabolism in the cytoplasm (MAO) or liver (COMT)
    • Primary metabolites are excreted in the urine as vanillylmandelic acid (VMA)

    Acetylcholine Synthesis and Metabolism

    • Choline and acetyl-CoA combine to form acetylcholine in the presence of acetyltransferase
    • Acetylcholine is stored in synaptic vesicles
    • After release, acetylcholine is rapidly metabolized by acetylcholinesterase to choline and acetate
    • Choline is taken up and recycled
    • Plasma cholinesterase metabolizes small amounts of acetylcholine

    Adrenergic and Cholinergic Receptors

    • Adrenergic receptors: alpha1, alpha2, beta1 (cardiac), beta2 (non-cardiac), dopamine1, and dopamine2
    • Cholinergic receptors: nicotinic (muscle, brain), muscarinic (M1, M2, M3, M4, M5)

    Aging and Autonomic Nervous System Dysfunction

    • Clinical manifestations include orthostatic hypotension, postprandial hypotension, and heat stroke
    • Due to decreased ability to adapt to stress and reduced number of adrenergic prejunctional terminals
    • Plasma epinephrine and beta-adrenergic receptor concentrations are unchanged
    • Response to beta-adrenergic stimulation is blunted in the elderly

    Ion Channels and Ligand-Gated Ion Channels

    • Ion channels open when the cell membrane depolarizes
    • Ligand-gated ion channels: acetylcholine, glutamate, GABA, and glycine

    Excitatory Neurotransmitters

    • Glutamate is the major excitatory amino acid neurotransmitter in the CNS
    • Non-selective channels: sodium-inward, calcium-inward, and potassium-outward
    • Metabotropic receptors are linked to G proteins modulating intracellular second messengers

    Inhibitory Neurotransmitters

    • GABA is the major inhibitory neurotransmitter in the brain
    • The GABA receptor binds two molecules of GABA
    • The channel opens, allowing chloride ions to enter the cell, leading to hyperpolarization
    • Target for: propofol, etomidate, and thiopental
    • Benzodiazepines allosterically increase the sensitivity of the receptor to GABA

    Glycine

    • The principle inhibitory neurotransmitter in the spinal cord
    • Glycine receptors are present in the brain
    • Increases chloride conductance

    Voltage-Gated Ion Channels

    • Channels which open and close in response to changes in voltage across cell membranes
    • Present in neurons, skeletal muscle, and endocrine cells
    • The site of local anesthetic action

    Receptor Concentration

    • Receptor populations are not static
    • Increased circulating concentrations of ligands often lead to a decrease in receptor density (down-regulation)
    • Drug-induced antagonism of receptors often results in an increase in receptor density (up-regulation)

    Synaptic Transmission

    • Site of transmission of an action potential from the presynaptic membrane to the postsynaptic membrane
    • Synaptic transmission begins with the arrival of an afferent action potential at the voltage-gated calcium channel
    • Influx of calcium occurs, binding to the release apparatus on axonal and vesicular membranes and triggers fusion of the vesicle to the cell membrane and exocytosis
    • Neurotransmitter is released into the synaptic cleft and binds to the postsynaptic membrane, stimulating an action potential in the dendrite of the efferent nerve

    Awareness and Recall

    • Defined as conscious memory of events during anesthesia
    • Administration of neuromuscular blocking drugs increases the risk of unintended awareness under general anesthesia
    • Memories can be explicit (conscious) or implicit (unconscious)
    • Occurs as often as 1-5/1000 cases
    • Often attributed to intentional or unintentional administration of low concentrations of administered anesthetic
    • Volatile inhalation agents suppress memory in a dose-dependent fashion
    • Indicators of awareness are masked by anesthesia drugs-opioids, beta blockers, neuromuscular blocking drugs
    • Heart rate, blood pressure, and skeletal muscle movement may indicate awareness
    • EEG interpretation and assessment of somatosensory evoked potential patterns may increase the ability to detect inadequate anesthesia

    Myelination

    • Myelination reduces energy required for repolarization
    • Nodes of Ranvier allow for saltatory conduction, increasing impulse speed
    • Action potentials are conducted from node to node, eliminating the need to travel the entire axon length

    Calcium Imbalance

    • Hypocalcemia leads to inability of Na channels to close
    • Hypercalcemia decreases cell permeability to Na ions, resulting in decreased excitability

    Potassium Imbalance

    • Hypokalemia results in membrane hyperpolarization and decreased excitability
    • Hypokalemia causes skeletal muscle weakness

    Effects of Local Anesthetics

    • Local anesthetics block Na channels
    • Local anesthetics decrease myocardial contractility

    Neurotransmission

    • After release, norepinephrine is either recycled or metabolized
      • Reuptake (80%)
      • Metabolism in the cytoplasm (MAO) or liver (COMT)
      • Primary metabolites are excreted in the urine as vanillylmandelic acid (VMA)
    • Acetylcholine is synthesized in the presence of acetyltransferase and stored in synaptic vesicles
    • After release, acetylcholine is rapidly metabolized by acetylcholinesterase to choline and acetate
      • Choline is taken up and recycled
      • Plasma cholinesterase metabolizes small amounts of acetylcholine

    Receptors

    • Adrenergic receptors: Alpha1, Alpha2, Beta1 (cardiac), Beta2 (non-cardiac), Dopamine1, Dopamine2
    • Cholinergic receptors: Nicotinic, Muscarinic (M1, M2, M3, M4, M5)

    Aging and ANS Dysfunction

    • Clinical manifestations include:
      • Orthostatic hypotension
      • Postprandial hypotension
      • Hypothermia
      • Heat stroke
    • Due to decreased ability to adapt to stress and reduced number of adrenergic prejunctional terminals
    • Plasma epinephrine and β adrenergic receptor concentrations are unchanged
    • Response to β adrenergic stimulation is blunted in the elderly

    Ion Channels

    • Ion channels open when the cell membrane depolarizes
    • Examples: Excitatory ligand-gated ion channels (Acetylcholine, Glutamate), Inhibitory ligand-gated ion channels (GABA)

    Excitatory Neurotransmitters

    • Glutamate is the major excitatory amino acid neurotransmitter in the CNS
    • Non-selective channels: Sodium-inward, Calcium-inward, Potassium-outward
    • Glutamate receptors: Ionotropic (NMDA, AMPA, Kainite), Metabotropic (linked to G proteins)

    Inhibitory Neurotransmitters

    • GABA is the major inhibitory neurotransmitter in the brain
    • GABA receptors: Ionotropic (opening channel allowing chloride ions to enter the cell), Metabotropic (linked to G proteins)
    • GABA is the target for: Propofol, Etomidate, Thiopental
    • Benzodiazepines allosterically increase the sensitivity of the receptor to GABA

    Evoked Potentials

    • Somatosensory EP: Stimulation of a peripheral nerve with a low-voltage current
    • Motor EP: Direct or indirect stimulation of the brain or spinal cord
    • Auditory EP: Arise from brainstem auditory pathways

    Awareness and Recall

    • Defined as conscious memory of events during anesthesia
    • Administration of neuromuscular blocking drugs increases the risk of unintended awareness under general anesthesia
    • Memories can be:
      • Explicit (conscious) spontaneous recall recognition memory
      • Implicit (unconscious) altered behavior or performance due to experiences that are not consciously recalled

    Bispectral Index (BIS)

    • Processed EEG combining the characteristics of various EEG waveforms to produce a dimensionless number between 1-100

    Glycine

    • Increases chloride conductance
    • Glycine receptors are present in the brain

    Voltage-Gated Ion Channels

    • Present in: Neurons, Skeletal muscle, Endocrine cells
    • Site of local anesthetic action

    Receptor Concentration

    • Receptor populations are not static
    • Increased circulating concentrations of ligands often lead to a decrease in receptor density (down regulation)
    • Drug-induced antagonism of receptors often results in an increase in receptor density (up regulation)

    Synapse

    • Site of transmission of an action potential from the presynaptic membrane to the postsynaptic membrane
    • Synaptic transmission begins with the arrival of an afferent action potential at the voltage-gated calcium channel
    • Influx of calcium occurs, binding to the release apparatus on axonal and vesicular membranes, triggering fusion of the vesicle to the cell membrane and exocytosis
    • Neurotransmitter is released into the synaptic cleft and binds to the postsynaptic membrane, stimulating an action potential in the dendrite of the efferent nerve

    Myelination

    • Dramatically reduces energy required for repolarization
    • Nodes of Ranvier allow for saltatory conduction, increasing impulse speed

    Implications of Calcium and Potassium Imbalance

    • Hypocalcemia leads to inability of Na channels to close
    • Hypercalcemia decreases cell permeability to Na ions – decreased excitability
    • Hypokalemia results in membrane hyperpolarization and decreased excitability – skeletal muscle weakness

    Depolarization

    • Depolarization is the process of making the membrane potential of a neuron less negative, moving towards a threshold potential.
    • During an action potential, the membrane potential rapidly depolarizes, reaching a threshold potential of around -55mV.

    Action Potential

    • Rapid depolarization is caused by a rapid influx of sodium ions through voltage-gated ion channels.
    • Depolarization is crucial for neurotransmission, as it allows the neuron to reach the threshold potential necessary for the release of neurotransmitters.

    Neurotransmission

    • When an action potential reaches the axon terminal, it triggers the release of neurotransmitters into the synapse.
    • The binding of neurotransmitters to receptors on adjacent neurons can cause depolarization, generating a new action potential.

    Electrophysiology

    • Depolarization is a critical component of electrophysiology, as it allows neurons to communicate with each other.
    • Depolarization of a neuron can be measured using electrophysiological techniques such as patch clamp recording or extracellular recording.
    • The speed and duration of depolarization can affect the frequency and pattern of action potentials.

    Ion Channels

    • Ion channels regulate the flow of ions across the cell membrane, playing a crucial role in depolarization.
    • Voltage-gated sodium channels are responsible for the rapid influx of sodium ions during an action potential.
    • The opening and closing of ion channels can be affected by various factors, including voltage, ligands, and phosphorylation.

    Excitability Threshold

    • The excitability threshold is the minimum amount of depolarization required to generate an action potential.
    • The excitability threshold is affected by various factors, including the concentration of ions, the presence of neurotransmitters, and the activity of ion channels.
    • Changes in the excitability threshold can affect the likelihood of an action potential being generated, and can be influenced by various physiological and pathological conditions.

    G Protein-Coupled Receptors

    • Components of G protein-coupled receptors include a receptor protein, 3 G proteins, and an effector mechanism.
    • Ligand binding to the surface protein triggers a conformational change.
    • This conformational change activates a G-alpha (G-α) coupled protein in the interior of the cell.
    • The G-α protein is attached to Guanosine Triphosphate (GTP).
    • The activated G protein transmits signals inside the cell.
    • G protein-coupled receptors can be either stimulatory or inhibitory.

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