McIlwain material
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- Isosmolar
- Two solutions with the same osmolarity
- isotonic
- Having the same osmolarity as ECF (300mOsm/L)
- Osmolarity
-
*molar concentration x number of dissociable particles
*inversely related to water concentration
*determined largely by Na+ and Cl-
*normal = 300 mOsm/L
*water flows from low osmolarity to high osmolarity -
Intracellular:
[K+]
[Na+]
[Cl-] -
[K+] = 120mM
[Na+] = 15mM
[Cl-] = 20mM -
Extracellular
[K+]
[Na+]
[Cl-] -
[K+]= 3.5-5.0mM
[Na+]= 135-145mM
[Cl-]= 100-111mM - Action of cardiac glycosides
-
Competitively inhibit K+ binding on the extracellular side of the Na+/K+ ATPase
(e.g. ouabain, digitalis) - Main functions of the Na+/K+ ATPase
-
1. Regulate cell volume
2. Establish RMP through K+ and Na+ concentration gradients.
3. Set up Na+ concentration gradient to power secondary active transporters. - Blocking the Na+/K+ ATPase causes...
- Cell swelling and lysis: Na+ continues to leak back into the cell and is accompanied by Cl-. The increased osmotic pressure results in an influx of water.
- Examples of Na+ powered secondary active transport (3)
-
1. Na+/glucose symporter in kidney tubules and gut.
2. Na+/amino acid transporter in most cells
3. Na+/Ca++ (3:1) antiporter in cardiac muscle. - Action of digitalis on cardiac tissues
- Partially inhibits Na+/K+ ATPase on cardiac myocytes. This reduces the Na+ concentration gradient and thus reduces Na+/Ca++ antiporter action. As a result Ca++ is accumulated in the cell. Increased Ca++ in cytoplasm and SR of cardiac muscle increases contractility.
- Equilibrium (for an ion)
- When the concentration gradient and electrical gradient are equal but opposite. There is no net flux of the ion.
- Nernst equation
- E = 58log([X1]/[X2])
- conductance
- The electrical equivalent of permeability which connotes the ease of passage of an ion through a membrane; equal to 1/resistance.
- Absolute refractory period (neural)
-
*No additional AP can be generated regardless of stimulus strength or frequency.
*Occurs because all Na+ channels are either all open already or all inactivated
*lasts from initiation to midway through repolarization - Relative refractory period
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*a new AP may be generated with a stimulus of greater strength or frequency
*lasts from midway through repolarization until after hyperpolarization
*enough Na+ channels have lost their inactivation, but it takes more to reach threshold - During an AP, why does Em never reach E-Na?
-
*Na+ channels are inactivated at a voltage less than E-Na
*K+ channels open at a voltage less than E-Na
*the driving force on Na+ decreases as the electrical gradient lessens - tetrodotoxin (TTX)
-
*Blocks Na+ channels from the outside
*prevents AP transmission
*can be used to decrease the amplitude of the AP - tetraethylammonium (TEA)
-
*blocks K+ channels from the inside
*prevents AP transmission
*can be used to increase the duration of an AP - Na+ channel structure
-
*4 domains (I-IV), each consisting of 6 transmembrane segments (S1-S6)
*voltage-sensor at S4 of each domain
*inactivation plug made from III-IV linker
*channel formed by S5-S6 linker of each domain - Passive electrical properties
-
*electrotonic - movement of e-
*decrements over distance
*conducts signals along inexcitable membranes
*conducts signals through areas where Na+ channels are blocked - Factors which change nerve conduction velocity
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*Increasing the axon diameter decreases the resistance and thus increases velocity
*increasing myelination increases velocity because it insulates against the loss of local current and decreases capacitance - Why are AP's in nerves "all or none"?
- Once a depolarizing stimulus has caused a membrane to reach threshold, all available V-gated Na+ channels will open.
- Electrical synapses
-
*very fast
*bi-directional
*typically made by gap junctions
*found in cardiac and smooth muscle, and some neurons - Lambert-Eaton Syndrome (LES)
-
*autoimmune disorder in which autoantibodies attack the presynaptic Ca++ channels
*this results in decreased ACh release
*correlated with small cell cancer of the lung - End plate potential
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*the potential that is generated when Na+ enters the motor end plate through ACh-gated channels
*graded response that is directly related to the [ACh]
*electrotonic signal that then depolarizes adjacent membrane enough to cause an AP - Myasthenia gravis
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*autoimmune disease where autoantibodies attack ACh receptors on the motor end plate
*treated with ACh-esterases - calsequestrin
- Used to increase the amount of Ca++ stored in the SR forty-fold
- Recruitment of motor units
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*occurs by the size principle: the smallest units are recruited first and the largest last
*is a means of increasing the power of a contraction - chemical synapses
-
*slower than electrical synapses
*unidirectional
*may be excitatory or inhibitory
*modulated by NT - repetitive stimulation of a single fiber
-
*a means of increasing strength of contraction
*involves the stretching of series elastic components (SEC)
*NOT due to increase of [Ca++]
*can lead to summation and tetanus - summation
- A fiber is not allowed to return to normal tension before being stimulated again
- tetanus
- A fiber reaches maximum tension
- excitation-secretion coupling
- The sequence of events beginning with the arrival of an AP and ending with the exocytosis of ACh.
- Neostigmine
-
*Inhibits ACh-esterase and thus increases [ACh] in the cleft
*can be used to terminate the action of non-depolarizing paralytic agents
*can also be paralyzing thru a depolarizing synaptic blockade - What is the mode of action of curare?
- It competes with ACH and prevents it from ginding the ACh receptor, thus keeping it closed. It is a reversible non-depolarizing blocker.
- succinylcholine
-
*ACh-R agonist which hold the receptor in the open state
*cause paralysis through chronic depolarization
*Na+ channels are unable to remove their inactivation plugs - alphabungaratoxin
- Irreversibly binds ACh-R in the closed state.
- What are the two main types of neuromuscular blocking agents?
- Those that inhibit the opening of the ACh-ion channel and those that hold the ACh-ion channel open.
- What would be 3 characteristics of an ideal muscle relaxant?
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1.Specificty for the NMJ
2.Rapid onset of action
3.Predictable duration -
T/F:
Curare affects only the ACh channels at the NMJ. - False: It can affect other ACh-mediated channels, this is a cause for ssome of its side effects.
- Why must curare be used with caution in patients with renal disease?
- It is excreted unmetabolized from the kidney, thus a decrease in renal function can allow accumulation of the active form.
- What is a side effect shared by succinylcholine and curare?
- They both stimulate release of histamine from mast cells.
- How is succinylcholine metabolized?
- It is hydrolyzed by a plasma pseudocholinestrase.
- How is succinlycholine able to produce cardiac arrhythmias? There are 2 ways.
-
*prolonged use can lead to hyperkalemia, which can lead to spontaneous depolarization of cardiac muscle cells
*can directly stimulate muscarinic ACh receptors in the sinus node - Can anticholinesterases like neostigmine be used to terminate the action of succinylcholine?
- No - actually they would prolong the action of a depolarizing blocker.