What are the intracellular and extracellular concentrations of sodium?
Intracellular = 15mM
Extracellular = 150mM
What are the intracellular and extracellular concentrations of Potassium?
Intracellular = 150mM
Extracellular = 5 mM
What are the intracellular and extracellular concentrations of Calcium?
Intracellular = 0.0001mM (free)
Extracellular = 1mM (free)
What are the intracellular and extracellular concentrations of Glucose?
Intracellular = 1mM
Extracellular = 5.6 mM
Definition:
The concentration of all osmotically active particles dissolved in water
Osmolarity
What are the non-penetrating solutes:
Ions (Na, K, Cl, Ca, etc.) and nutrients
What are the penetrating solutes?
Glucose and Urea
Definition:
A measure of the ability of a solution to induce shrinkage or swelling when placed in contact with specified cells
Tonicity
Water will flow down its concentration gradient from a solution with ( ) osmolarity to a solution with ( ) osmolarity
Low to High
Definition:
The pressure that must be exerted on the cell to prevent the flow of water due to the solute concentration difference
Osmotic Pressure
What effect does a high osmolarity (high solute concentration) have on osmotic pressure?
Higher osmolarity = higher osmotic pressure
Type of membrane potential for a given ion where the driving force of the concentration gradient balances the driving force of the electrical gradient. There is no net movement of the ions across the membrane
Equilibrium Potential
What is the equilibrium potential of Potassium?
-89 mV
What is the equilibrium potential of Sodium?
+60 mV
What is the equilibrium potential of Chloride?
-72 mV
At rest, the conductance of which ion is approximately 50x that of which other ion?
At rest, the conductance of potassium is approximately 50x greater than sodium
Osmolarity Calculations:
150 mM NaCl = ?
5 mM KCl = ?
1 mM CaCl2 = ?
2 mM MgCl2 = ?
10 mM Glucose = ?
150 mM NaCl = 300 mOsm
5 mM KCl = 10 mOsm
1 mM CaCl2 = 3 mOsm
2 mM MgCl2 = 6 mOsm
10 mM Glucose = 10 mOsm
Resting membrane potential
-70 mV
Definition:
The difference between the membrane potential and the equilibrium potential
Driving Potential
Events during an Action Potential (7):
1. Neuron at resting potential
2. Depolarization of neuron causes membrane to reach threshold potential and activate voltage-
gated sodium channels
3. Influx of sodium leads to further depolarization of neuron. Depolarization produced by influx of
sodium causes delayed opening of potassium channels
4. Sodium channels inactivate after 1 msec
5. Efflux of potassium causes repolariztion of neuron
6. Overshoot of hyperpolarization is due to high potassium conductance
7. Potassium channels close and membrane potential returns to resting potential
What is the threshold potential?
-55 mV
What 2 factors cause an increase in conduction velocity of an action potential?
Myelination and increasing the axon diameter
Where does membrane potential peak?
+30 mV
What molecule is responsible for vesicle docking, and holds vesicles in place?
SNAREs
What digests SNAREs, inhibiting neurotransmitter release?
Botulinum Toxin
This type of potential is due to the release of one vesicle of ACh. Depolarizes the postsynaptic membrane by 0.4 mV
Miniature Endplate Potential (MEPP)
This type of potential is produced by activation of nicotinic receptors by ACh. Due to an increase in both sodium and potassium conductance through nicotinic receptors. Magnitude is 40 mV. Caused by the release of over 200 synaptic vesicles
End-plate Potential (EPP)
Type of summation:
Increasing the frequency of the action potentials of a single neuron will increase the amplitude of graded potentials. The second action potential arrives before the membrane potential has returned to baseline
Temporal Summation
Type of summation wherein multiple action potentials arrive at the same location at the same time
Spatial Summation
Drug used in the inhibition of neurotransmission that serves to blockade action potentials
Lidocaine
Drug used in inhibition of neurotransmission that serves to inhibit the synthesis of neurotransmitters
alpha-methyl-para-tryosine
Drug used in the inhibition of neurotransmission that inhibits the storage of neurotransmitters
reserpine
Drug used in inhibition of neurotransmission. It is an N-type calcium channel blocker. It is released from sea snails & used for chronic pain.
Ziconotide
This drug is the nicotinic receptor antagonist
Curare
This drug is the muscarinic receptor antagonist
Atropine
This drug is the beta-adrenergic receptor antagonist
Propranolol
Drug used to inhibit neurotransmitter metabolism with organophosphates that inhibit acetylcholine esterase
Physostigmine
Monoamine Oxidase (MAO) metabolizes which three catecholamines?
Dopamine, Norepinephrine, Epinephrine
Monoamine Oxidase (MAO) metabolizes which indolamine?
Serotonin
This drug is used as an antidepressant and in Parkinson's disease
Selegiline
Catechol-O-methyltransferase (COMT) inhibitors increase levels of which catecholamines in synaptic clefts?
Dopamine, Norepinephrine, Epinephrine
Which two dugs are known as catechol-O-methyltransferase (COMT) inhibitors and are used for Parkinson's disease?
Tolcapone and Tasmar
What drug blocks dopamine reuptake?
Cocaine
What drug blocks serotonin reuptake?
Fluoxetine (Prozac)
Which drug is an alpha-adrenergic agonist?
Phenylepherine
These drugs bind to GABA receptors and increase the frequency of the GABA-stimulated chloride channel opening
Benzodiazpines (Diazepam, Valium)
Definition:
Causes the reduction or elimination of pain
Analgesia
Definition:
This causes a reduction or elimination of sensation. Includes mechanical sensation (touch, pressure, vibration) and painful stimuli (nociception) and temperature
Anesthesia
Type of local ester anesthetic. First synthetic local anesthetic. Used as an infiltration anesthetic and occasionally for nerve blocks for diagnostics. Low potency, slow onset, short duration of action. Has been replaced by newer agents
Procaine (Novocain)
Type of local ester anesthetic. Fast onset, short acting, rapidly metabolized. Commonly used for labor and delivery and C-sections. Has generally replaced procaine as a short acting local anesthetic
Chloroprocaine (Nesacaine)
Type of ester anesthetic. More potent and longer duration than procaine due to slow metabolism. Widely used for spinal anethesia.
Tetracaine (Pontocaine)
Type of local ester anesthetic. Used only as a topical local anesthetic. A weak acid, so it exists primarily as uncharged form at physiological pH. Has rapid onset and effects last 30-60 minutes. Found in many over the counter preparations.
Benzocaine
Type of local ester anesthetic. First local anesthetic. Has both local anesthetic and potent vasoconstrictor properties (due to blockade of catecholamine reuptake at vascular smooth muscle). Used as a topical anesthetic primarily for analgesia of the upper respiratory tract as well as nose and ear procedures. Its vasoconstrictor properties limit the bleeding during the procedures and improve surgical visualization.
Cocaine
An amide local anesthetic. The most widely used local anesthetic. Produces fast, intermediate lasting local anesthetic. Usually given as a 2% solution with epinephrine
Lidocaine (Xylocaine)
A widely used amide local anesthetic. Has a long duration of action. Has a higher cardiotoxic effect than lidocaine.
Bupivicaine (Marcaine, Sensorcaine)
Intermediate acting local amide anesthetic with properties similar to lidocaine, but with a slightly higher therapeutic index and a slightly longer (20%) duration of action. Slightly more toxic in neonate and should not be given for obstetrical anesthesia. Not an effective topical anesthetic.
Mepivicaine (Carbocaine, Isocaine)
Local amide anesthetic with long duration. Has less cardiotoxic effects than bupivicaine
Ropivacaine (Naropin)
Method of Anesthetic Administration:
Anesthetic is administered by applying the local anesthetic to mucous membranes of the nose, mouth, throat, tracheobronchial tree, esophagus, and genitourinary tract. Anesthetics are rapidly absorbed into the blood after this type of application, and thus has a higher risk for toxic reactions.
Topical Anesthetic
Method of Anesthetic Administration:
Extravascular placement of local anesthetic in area to be anesthetized. The local anesthetic is injected into the area without consideration of the course of the cutaneous nerves. Can produce effective anesthesia without disrupting bodily functions. A large amount can be given to a small area. Lidocaine is the most commonly used for this type of administration.
Infiltration Anesthesia
Method of Anesthetic Administration:
Injection of a local anesthetic into or around a peripheral nerve or nerve plexsuses. Produces a greater area of anesthesia than infiltration anesthesia. Anesthesia of peripheral mixed nerves will cause loss of sensation as well as blockade of somatic motor neurons resulting relaxation of skeletal muscles. The outer portion of a peripheral nerve contains neurons from proximal areas while the inner portion of the nerve contains neurons from more distal areas. The anesthesia will occur several centimeters distal to the site of injection. Long acting anesthetics, bupivacaine and ropivacaine, are primarily used for this type of administration.
Nerve Block Anesthesia
Method of Anesthetic Administration:
Injection of local anesthetic into the cerebrospinal fluid (CSF) in the lumbar space. This route of administration produces anesthesia over a large portion of the body with minimal plasma levels. The anesthetic is injected below the termination of the spinal cord, approximately at the second lumbar vertebra, and above the termination of the thecal sac in the sacrum. The lumbar and sacral nerve roots are bathed in CSF and there is a large volume of CSF where drug can be injected with minimal chance of producing nerve trauma. Used for surgery to abdomen, lower extremities, and perineum. Long acting anesthetics, bupivacaine and ropivacaine, are used.
Spinal Anesthesia
Type of Anesthetic Administration:
Local anesthetics are injected into the epidural space. The drugs can be administered in the caudal, lumbar, thoracic, and cervical regions of the spinal cord. The site of action is on the nerve roots. New technology allows for chronic administration through catheters placed in the epidural space. Local anesthetics are more readily absorbed into the circulation using this than spinal. Commonly used during labor and delivery. Can cross the placenta into the neonate. Lidocaine, Ropivacaine, and bupivacaine are used.
Epidural Anesthesia
Definition:
This agent is used to block propagation of action potentials from sensory neurons into the spinal cord to releave nociception
Local Anesthesia
Definition:
These are frequently included in the formulations with local anesthetics. Purposes are to decrease the absorption of the local anesthetics into the circulation, prolong the duration of action, and decrease toxicity. Epinephrine is the common one used.
Vasoconstrictors
What are the five dose-dependent effects of Lidocaine?
What are the effector organs of the autonomic nervous system (4)?
1. Cardiac Muscle
2. Smooth Muscle
3. Glands
4. GI Neurons
Which type of ganglionic neurons are myelinated, and secrete acetylcholine as their neurotransmitter?
Preganglionic Neurons
Where are the cell bodies of preganglionic neurons located, and where do they send their axons?
Located in CNS and send axons to peripheral ganglia where they innervate postganglionic neurons
Where are the cell bodies of postganglionic neurons located, and where do they send their axons?
Located in peripheral autonomic ganglia, and send axons to the target organ
Which type of ganglionic neurons are unmyelinated and secrete acetylcholine or norepinephrine as their transmitter?
Postganglionic Neurons
These cells are located in the adrenal medulla, and receive innervation from preganglionic sympathetic neurons. These secrete epinephrine and norepinephrine in proportions of 80% and 20%, respectively.
Specialized Chromaffin Cells
What is the cholinergic neurotransmitter?
Acetylcholine
What is the primary neurotransmitter released by sympathetic postganglionic neurons?
Norepinephrine
Is epinephrine released from sympathetic postganglionic neurons?
No, it is only released as a hormone from chromaffin cells in the adrenal medulla
Where are adrenergic receptors found?
On effector organs or tissues
What type of effects (excitatory or inhibitory) do alpha-adrenergic receptors produce?
Excitatory, except in the GI tract, where they produce inhibitory effects
Which type of receptor are located on presynaptic noradrenergic terminals and act as autoreceptors?
Alpha2-adrenergic receptors
What type of effects (excitatory or inhibitory) do beta-adrenergic receptors produce?
Inhibitory, except in the heart, where they produce excitatory effects
Where are beta1-adrenoreceptors primarily found, and what type of effects do they produce?
Found primarily in the heart, and produce excitatory effects on the heart
What type of receptors are located primarily in brown adipose tissue, are excited by circulating epinephrine, and mediate lipolysis when stimulated?
Beta3-adrenoreceptors
Definition:
Organs which receive innervation from both the sympathetic and parasympathetic systems have which type of innervation?
Dual Innervation
Definition:
This occurs in dual innervated organs when the sympathetic and parasympathetic systems work together to produce an effect
Functional Synergism
Definition:
A continuous resting level of autonomic neural activity to an organ or tissue. This means, in effect, that there is almost always some autonomic nerve activity from both the SNS and PNS under all types of conditions
Tonic or Basal Nerve Activity
What is the SYMPATHETIC receptor and response (effect) on the EYES?
Alpha-1; Mydriasis (contract radial muscle)
What is the PARASYMPATHETIC receptor and response (effect) on the EYES?
Muscarinic; Miosis (contract circular muscle)
What is the SYMPATHETIC receptor and response (effect) on the CARDIOVASCULAR SYSTEM?
Beta-1; excitatory
What is the PARASYMPATHETIC receptor and response (effect) on the CARDIOVASCULAR SYSTEM?
Muscarinic; inhibitory
What is the SYMPATHETIC receptor and response (effect) on the BLOOD VESSELS?
alpha-1, alpha-2, and beta-2; Aphas excite, betas inhibit
What is the PARASYMPATHETIC receptor and response (effect) on the BLOOD VESSELS?
No effect
What is the SYMPATHETIC receptor and response (effect) on the LUNGS?
beta-2; inhibitory
What is the PARASYMPATHETIC receptor and response (effect) on the LUNGS?
Muscarinic; Excitatory
What is the SYMPATHETIC receptor and response (effect) on the GI TRACT?
Alphas and Betas; inhibitory
What is the PARASYMPATHETIC receptor and response (effect) on the GI TRACT?
Muscarinic; inhibitory
What is the SYMPATHETIC receptor and response (effect) on the REPRODUCTIVE TRACT?
Alpha-1; ejaculation
What is the PARASYMPATHETIC receptor and response (effect) on the REPRODUCTIVE TRACT?
Muscarinic; erection
Definition:
A reflex used to control short term changes in blood pressure
Baroreceptor Reflex (Baroreflex)
Where are receptors that sense blood pressure located?
At the carotid sinus and the aortic arch
What is one contributory mechanism of hypertension?
An increase in the tonic or basal level of sympathetic tone to the heart and/or blood vessels
Definition/Disorder:
A tumor of the chromaffin cells in the adrenal gland. Accounts for only 0.1% of hypertensive patients
Pheochromocytoma
Definition/Disorder:
A drop in arterial pressure of 30 mmHg or more upon standing. Dizziness is felt upon standing due to an inadequate perfusion of the CNS. Due to an inadequate reflex control of blood pressure.
Postural (Orthostatic) Hypotension
Definition/Disorder:
This results from loss of sympathetic innervation to the head; the damage that produces this can occur in any part of the total pathway from hypothalamus to spinal cord and back up to the head. There are three classic signs of this syndrome: Miosis, Ptosis, and Anhydrosis
Horner's Syndrome
Definition:
Constriction of the pupil of the eye to less than or equal to 2 mm
Miosis
Definition:
Drooping of the eyelid
Ptosis
Definition:
Loss of sweating
Anhydrosis
Definition/Disorder:
This can occur in diabetics due to degeneration of small nerve fibers. The precise cause is not certain, but may be a problem of adequate blood perfusion and/or metabolic problems in neurons. A wide variety of problems can result, such as impaired swallowing, delayed gastric emptying, diarrhea, orthostatic hypotension, bladder dysfunction, and erectile dysfunction
Autonomic Diabetic Neuropathy
Definition/Disorder:
Some patients with a spinal cord lesion at the T6 level or above may develop this condition. The major characteristic of this condition is extremely high blood pressure. Multiple stimuli may evoke the hypertension, the most common of which being bladder distension and distension of the colon and/or rectum, but other stimuli such as touching the lower abdomen adn pregnancy may also evoke it. Presumably the plasticity that occurs in the spinal cord after a spinal cord injury allows sensory input to produce an abnormally large sympathetic outflow
Does inhibition cause an increase or decrease in heart rate?
Decrease
Does excitation cause an increase or decrease in heart rate?
Increase
Does constriction respresent an excitatory or inhibitory effect on blood vessels?
Excitatory
Does dilation respresent an excitatory or inhibitory effect on blood vessels?
Inhibitory
Definition:
These neurons send status reports of the organs to the CNS. All organs have them
Sensory Neurons
Single innervation is only seen where?
blood vessels
What activates non-innervated receptors?
Circulating epinephrine
Definition:
Cyndrilical bundles of thick and think filaments that form muscle fiber; hexagonal array of thick and thin filaments
Myofibrils
What are A-bands composed of?
Overlapping myosin and actin
What are I-bands composed of?
Actin alone
Do I-bands change length during contraction?
Yes, they shorten
Do A-bands change length during contraction?
No
Definition:
The force exerted by muscle on an object
Tension
Definition:
The force exerted by an object on muscle
Load
Definition:
A type of contraction wherein the load is equal to or greater than tension, there is no shortening, and there is a constant length of muscle. Measure tension
Isometric Contraction
Definition:
A type of contraction wherein the tension is greater than the load, the muscle shortens, and there is constant tension. Measures length
Isotonic Contraction
As load decreases, what happens to the distance of shortening?
Decreases
What are the two factors that determine tension of whole muscles?
1. Number of fibers per motor unit
2. Recruitment--activation of more motor units
Definition:
Type of skeletal muscle that deals with metabolism. Has numerous mitochondria, rely on oxidative phosphorylation for ATP, highly vascularized, contain myoglobin to transport and help store O2 in cells, "red" muscle due to myoglobin
Oxidative Fibers
Definition:
Type of skeletal muscle that deals with metabolism. Has high amounts of glycolytic enzymes, few mitochondria, large stores of glycogen, little myoglobin, poorly vascularized, pale color, "white" muscle fibers
Glycolytic Fibers
Definition:
Type of skeletal muscle that has low ATPase activity, and slow cross-bridge cycling
Slow-Twitch Fibers
Definition:
Type of skeletal muscle that has high ATPase activity, and rapid cross-bridge cycling
Fast-Twitch Fibers
What are the three characteristics of muscle fiber types?
1. Myosin ATPase activity (slow-twitch or fast-twitch)
2. Metabolism (oxidative or glycolytic)
3. Fiber Size (small, medium, or large)
What is the order of recruitment of muscle fiber types?
1. Type I
2. Type IIa
3. Type IIb
Definition:
Decrease in tension after continuous stimulation
Fatigue
Which muscle fiber type fatigue the slowest?
Type I
Which muscle fiber type fatigue the fastest?
Type IIb
What is the present theory of the mechanism of muscle fatigue?
Accumulation of inorganic phosphate (PO4) during muscle activity inhibits cross bridges binding to actin
Definition:
Bundles of muscle fibers
Fascicles
Do the thick and thin filaments change length during muscle contraction?
No, shortening is due to thin filaments sliding over the thick filaments
What are the four steps of the cross bridge cycle in muscle contraction?
1. "Energized" cross bridge attaches to actin
2. Pi is released and cross bridge rotates and pulls the thin filaments towards the center of the sarcomere; ADP is released from myosin head
3. ATP binds to myosin head; cross bridge detaches
4. Hydrolysis of ATPase on myosin energizes cross bridge
What are the two roles of ATP in the cross bridge cycle?
1. Hydrolysis of ATP "energizes" the cycle
2. Binding of ATP breaks the linkage
*Lack of ATP produces rigor mortis--the stiffness seen in rigor mortis is due to crossbridges staying bound to actin
What effect does the binding of calcium to troponin produce?
Causes a conformational change in troponin, which allows tropomyosin to move off of the actin binding site, leaving it open for myosin cross-bridges to bind, leading to muscle contraction
At what load to you get maximum velocity?
Zero Load
What type of contraction is seen as maximum load
No contraction (isometric twitch)
What does cancer cachexia cause?
An irreversible loss of muscle mass
What change in fiber type can happen with endurance exercise?
Fast-glycolytic fibers (type IIb) can increase oxidative enzymes and become fast oxidative fibers (Type IIa)
What change in fiber type can happen with high intensity exercise?
Fast oxidative fibers (type IIa fibers) can increase glycolytic enzymes and become fast glycolytic fibers (type IIb)
What is the function of dense bands in smooth muscle?
Attach actin to membrane
Definition:
Low resistance electical pathways between cells in smooth muscle
Gap Junctions
Which branch of the nervous system provides the innervation for smooth muscle?
Autonomic Nervous System
Does smooth muscle fatigue?
No
What does calcium bind to in smooth muscle?
Calmodulin
What does the calcium-calmodulin complex bind to in smooth muscle?
Myosin Light-Chain Kinase
What are the seven steps of smooth muscle PHASIC contraction?
1. Calcium binds to calmodulin
2. Calcium-calmodulin complex binds to myosin light-chain complex
3. Myosin light-chain kinase phosphorylates myosin with ATP
4. Activated myosin then binds to actin and begins the cross bridge cycle
5. Sequestration of calcium causes inactivation of myosin light chain kinase
6. Myosin is dephosphorylated and cross bridge cycle ceases
7. If myosin is detached from actin when myosin is dephosphorylated by phosphatase, then the muscle relaxes
What differences are seen in TONIC contraction of smooth muscle?
1. Activation of cross bridge cycle by CaCAM activation of myosin light chain kinase
2. If myosin is attached to actin when myosin is dephosphorylated, then the myosin remains attached to actin and a sustained contraction ocurrs (latch state). The myosin will detach when myosin is rephosphorylated by MLCK
Definition/Smooth Muscle Type:
This smooth muscle type has a high degree of innervation. Individual muscle cells contract independently of their neighbor. "Multiunit" refers to the muscles acting independently as multiple units. There is no organized neuromuscular junction. Neurotransmitter is released from variscosities adn affects fewer cells.
Multiunit Smooth Muscle
Definition:
The synapse between autonomic nerves and smooth muscle
Neuroeffector Junction
Definition/Smooth Muscle Type:
In this type of smooth muscle, smooth muscle cells contract with other cells. There are numerous gap junctions to allow electrical coupling between smooth muscle cells. Coordinated contractions spread across the muscle by propagation of electrical activity through gap junctions. This smooth muscle type is found in the muscles lining the hollow organs.
Single Unit Smooth Muscle (aka Unitary Smooth Muscle)
What three factors causes the velocity of smooth muscle contractions to be 10 to 100 times slower than skeletal muscle?
1. the ATPase for the myosin is slower in smooth muscle than in skeletal muscle
2. the calcium for smooth muscle comes from extracellular sources
3. the cross bridge cycle depends on the degree of phosphorylation of the myosin
(the greater percentage of myosin phosphorylated, the faster the velocity of contraction)
Pharmomechanical coupling in smooth muscle is contraction without changes in membrane potential. Receptor activation leads to increased levels of what molecule? What is released from SR?
Leads to increased inositol triphosphate (IP3) and release of calcium from SR
Definition:
Contraction of smooth muscle without changes in membrane potential
Pharmacomechanical Coupling
beta 2 receptors are in
lungs, blood vessels
Beta 2 receptors activity
not active naturally (can be pharmacologic targets)
muscles that make hair stand up
pilomotor
viscous saliva comes from
sympathetic innervation of salivary glands
What does beta 1 agonist do?
Increase heart rate
Increase ventricular contraction
Increase conduction velocity
Classic nicotinic receptor blocker
curare
Preganglionic efferent neurotransmitter for autonomic nervous system
acetylcholine
Whenever there is reciprocal innervation who wins, parasympathetic or sympathetic?
Parasympathetic
sympathetic ganglia location
close to spinal cord
regional blood vessels - skin - what receptor is sparse?
very very few non innervated beta 2 receptors
True or False:
Curare also blocks autonomic ganglia
True at higher doses
Example of organ that has reciprocal innervation
pacemaker part of the heart
True or False:
Epinephrine will cause vasodilation in muscles
True, beta 2 receptors common there
Parasympathetic ganglia location
close to effectors
baroreceptors are what kind of receptors?
stretch
eccrine sweat glands are activated by what neurotransmitter
acetylcholine (sympathetic)
most important role of epinephrine in the body in fight or flight (according to Koss)
