Test 1 Study Table Flashcards

1
Q

Compare contraction of smooth vs skeletal muscle

  • voluntary vs involuntary
  • note ligands for receptors
  • role of Calcium
  • main determinant of force
A

Smooth-

  • non-voluntary
  • preganglionic- ACh
  • postganglionic- ACh (parasympathetic), NE (sympathetic)
  • Calcium (depolarizing, lesser role than in sk muscle)
  • MLCK/MLCP- main determinant of force

Skeletal-

  • mostly voluntary (somatic)
  • NMJ- Nicotinic Cholinergic (ACh)
  • Calcium is the main determinant of force
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2
Q

Regulation of muscle contraction in smooth vs skeletal muscle

A

Smooth:

  • Regulation of MLC (K or P) at any given Ca concentration
  • T-type Ca channels help regulate vascular tone
  • Autonomics

Skeletal:

  • contraction force is dependent on intracellular Ca concentration
  • motor units (one neuron & all the fibers it innervates- all the same type)
  • Fiber type
  • Availability of ATP
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3
Q

Describe the steps of the smooth muscle slow wave

A

T type voltage gated Ca channels open —> L type (voltage gated) Ca channels open) —> AP spike —> Ca influx, rise in internal Ca concentration —> Ca dependent K channels open —> slow hyperpolarization —> Voltage gated Ca channels close and internal Ca concentration decreases

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4
Q

Describe histology of smooth muscle

A
  • one nucleus (vs multiple in skeletal)
  • spindle shaped cells
  • smaller in comparison to skeletal
  • caveolae (instead of T tubules) - contain voltage gated Ca channels, increase surface to volume ratio
  • NO: sarcomeres, striations, or T tubules
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5
Q

Both skeletal and smooth muscle have

A
  • thick (myosin) and thin (actin) filaments

- SR (more elaborate in skeletal muscle)

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6
Q

Multi-unit vs single unit smooth muscle

A

Multi-unit: each smooth muscle receives synaptic input from it’s own varicosity. Gives finer control.
- Found in iris smooth muscle, ciliary muscle, and piloerector muscle in the skin (goose bumps)

Unitary (visceral): most common. Contains gap junctions that allow an organ to respond as a unit. Such as propagation of food through intestine, movement of blood through vessels
- Found in intestines, utereus, ureter, small arteries/veins

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7
Q

Smooth muscle contraction

A

Need elevated Ca inside the cell in order to initiate a series of events that will lead to smooth muscle contraction
Ca binds to Calmodulin, creating Ca-Calmodulin complex
Ca-Calmodulin complex binds to and activates MLCK
MLCK phosphorylates myosin at light chains activating it!
- actual contraction occurs when activated (phosphorylated) myosin binds to actin and causes contraction

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8
Q

Smooth muscle relaxation

A

No Ca in the sarcoplams
Ca is pumped out by:
- PMCA, Na/Ca exchanger: from sarcoplasm to ECF
- SERCA: sarcoplasm to sr
MLCK inactive
MLCP removes phosphate from myosin
Dephosphorylation of myosin while it is attached to actin results in a slow detachment - Latch state

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9
Q

Energy sources of muscle: smooth vs skeletal

A

Smooth:

  • mostly aerobic (mitochondria)
  • No creatine phosphate
  • sustained contraction with minimal use of ATP (latch phase)
  • Slow Ca regulation (slow contractions)

Skeletal:

  • Aerobic or anaerobic (depends on type of fiber)
  • Cr-Ph stores phosphate for contractile use
  • Fast contraction and relaxation
  • Force is dependent on SR Ca concentration
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10
Q

Calcium regulation in muscle

A

Smooth- up to 50% from IF

Skeletal- 99% SR

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11
Q

What is responsible for bringing skeletal muscle at the NMJ to threshold potential?

A

Nicotinic cholinergic receptors

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12
Q

An EPSP at a smooth muscle cell depolarizes it to threshold what action happens next?

A

Voltage gated Ca++ channels open

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13
Q

An EPSP at a skeletal muscle cell depolarizes it to threshold what action happens next?

A

Voltage gated Na channels open

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14
Q

Autonomic receptors

A

Postganglionic neuron cell body- nicotinic neuronal cholinergic receptor (Nn)

Target cell-
Sympathetic- alpha & beta adrenergic
PSNS- M1, M2, M3 muscarinic

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15
Q

Adrenergic R’s: pathway, function

A

Alpha1- PLC pathway. Increases smooth muscle contraction
Alpha2- Gi —> inhibit AC —> dec cAMP —> favors smooth muscle contraction (can block gastric secretion and insulin release)
Beta- Gs —> stimulate AC —> inc cAMP —> PKA —> inhibits MLCK —> smooth muscle relaxation

Beta 1- heart. Increase HR & increase cardiac contractility
Beta 2- smooth muscle relaxation
Beta 3- lipolysis in adipose tissue

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16
Q

Muscarinic Receptor

A

M1- ganglionic slow EPSP in CNS
M2- Decrease HR (IPSP)
*** M3- smooth muscle contraction, GI secretion, Endothelial NO secretion
- overstimulation causes asthma

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17
Q

Proteosome system

A

Proteins marked for degradation by proteosome when lighted to Ub

DUB enzyme, less protein enters a proteasome and effectively not all of the marked proteins get destroyed

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18
Q

_______ is involved in signal transduction

A

Phosphatidylinositol

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19
Q

What influences fluidity of a plasma membrane?

A

Cholesterol and degree of saturation

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20
Q

Fick’s law

A

Diffusion rate = -PA (Ci - Co)

P= permeability

  • membrane resistance
  • membrane thickness
  • size and solubility of the molecule
  • Temperature

A= surface area

Ci-Co = concentration gradient across the membrane

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21
Q

Facilitated diffusion exhibits ___________________ and requires _______________

A
  • saturation
  • specificity
  • competition

A Protein channel

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22
Q

Transmembrane ion channels

A

Antiport:
Na/H
3Na/Ca

Symport:
Na/K/2Cl
Na/Cl
Na/HCO3
Na/PO4
Na/amino acids
23
Q

Receptor mediated endocytosis

A
Ligand binds receptor
Formation of a coated pit with clathrin 
Formation of a coated vesicle 
Vesicle uncoating
Uncoated vesicle fuses with lysosomes
Recycle clathrin & endocytose product
24
Q

2,4-Dinitrophenol (DNP)

A

Uncoupled oxidative phosphorylation by ruining the hydrogen gradient at the mitochondrial membrane resulting in production of heat with no ATP produced
- used to be a diet pill

25
Sodium Azide
Inhibits cytochrome C oxidase (complex IV) by binding to the heme cofactor - similar to cyanide poisoning Affects organs undergoing high rates of respiration
26
Body water compartments
``` TBW (total body water) is 60% of BW (body weight) 40% intracellular 20% extracellular - 4% plasma - 16% interstitial fluid ``` ``` ECF= 1/3 TBW or 20% BW ICF= 2/3 TBW or 40% BW ```
27
Plasma osmolality
Plasma osmolality = 2 Na + glucose + urea
28
Plasma toxicity
Plasma toxicity = 2 Na + glucose
29
Regulatory volume increase
A cell is in hypertonic solution, after the cell shrinks in size It will undergo RVI - activate Na/H exchanger —> Cl-HCO3 exchanger (H out, bicarbonate in) - activate Na/K pump - activate Na/K/2Cl cotransporter - Chronic response- generation of idiogenic osmoles (example sorbitol)
30
Regulatory volume decrease
When a cell is in a hypotonic solution, after swelling, it will undergo RVD - activate K/Cl symport
31
Oncotic pressure
The osmotic pressure generated by the presence of protein (albumin) in blood vessels keeping fluid in vessels and out of interstitial fluid
32
Give 3 possible problems in fluid regulation
Hypoalbumenia- secondary to liver disease/damage, or malnutrition CHF- increased hydrostatic pressure Impaired lymphatic drainage
33
CFR equation
``` CFR= hydrostatic - oncotic CFR= Kf (Pc-Pisf) - sigma (onc c- onc isf) ```
34
Hydrostatic pressure
The pressure exerted by a fluid at equilibrium at a given point within the fluid, due to the force of gravity. Pushes fluid out of the vessel
35
Transcellular
Utilizes proteins and channels which are restricted to either the basolateral or apical surface
36
Paracellular
Utilizes electrochemical gradient and occurs through tight junctions Positive charge created by certain channels pushes Ca and Mg towards paracellular transport Not in the distal aspects of nephron
37
Kidney transport
Basolateral: - Na-K ATPase (3Na to blood, 2K into cell maintains gradient) - Cl channel (Cl into blood) Apical: - Na/K/2Cl symporter (into cell) - K channel (into lumen) - Ca, Mg, and H2O paracellular K+ pushes Mg and Ca back into the blood via paracellular transport Diuretics block leaky channels so water flows into lumen (to ion inc concentration). Pee out water
38
Sweat gland
Acinus (deep)- water and Cl channel. Na paracellular Duct: CFTR and ENac channel so less salty sweat
39
Cystic fibrosis
Mutation in CFTR gene Homozygous- more salty sweat Heterozygous- less salty sweat
40
Aldosterone
Diffuses through the cell membrane where once it forms a complex with a dimerized receptor in the cytoplasm, then enters the nucleus where it acts as a TF to stimulate cellular components to assist in positive water balance Receptor intracellular bound to HSP - aldosterone binds mineralocorticoid R —> TF in nucleus —> positive water balance 1- Increase Na/K ATPase 2- Increase Na leak channel 3- decease permeability of tight junctions
41
Dyneien and kinesin
Microtubule axoplasmic transport - Retrograde transport - Dynein - Orthograde transport- Kinesin
42
Normal Ca levels and result of abnormal levels
8.5-10.5 Extracellular Ca opens Na channel Hypocalcemia- increased opening of Na channel —> tetany Hypercalcemia- decreased opening of Na channel —> weakness
43
Significance of Cytochrome p450
Different genetic expressions of CYP can result in different drug metabolism Therapeutic doses of a drug may be toxic or not effective depending on CPY genetics of the individual
44
Role of Glutamate
Release from UMN (CNS) to stimulate LMN (PNS) ACh then released from LMN
45
Demyelinating disease
Leads to leakage/opening of K channels, slowing AP
46
Relative susceptibility of mammalian nerve fibers to conduction block
C- slowest and smallest (sensory) most susceptible to local anesthetics A- motor fibers, most myelinated largest. Least susceptible to local anesthetics
47
Name 3 inhibitory neurotransmitters
GABA Glycine Substance p
48
GABA a vs GABA b
GABA-A: ionotropic results in opening of Cl anion channel. Brings membrane to Chloride equilibrium potential -89. Produces fast IPSP. GABA-B: metabotropic. Results in opening of K channels via GPCR. Brings membrane closer to K eq potenital -95
49
Myasthenia Gravis
Autoimmune disease Antibodies bind and eventually reduce the number of ACh receptors Increased muscle weakness as day progresses Tx- Pyridostigmine (AChE inhibitor)
50
Lambert Eaton
Autoimmune disease Against voltage gated Ca channels Sx- weakness in limbs, not in ocular muscles EMG compound motor action potentials (CMAP) - repetitive stimulation increases contraction Tx- Pyridostigmine
51
Neuromodulators
Proteins that can increase or decrease effect of neurotransmitters Can change- response to nt, synthesis of nt, amount of nt released in response to a stimuli Cannot change- rate of AP firing, conduction of nerve impulses Ex. Adenosine, beta-endorphin, substance p
52
Malignant hyperthermia
Autosomal dominant defect in RYR - risk with depolarizing agent Succinylcholine Over secretion of Ca —> sustained muscle contraction and generation of excess body heat Tx- Dantrolene (RYR antagonist)
53
Fiber types
Type 1- slow twitch Type 2A- fast twitch oxidative Type 2B- fast twitch glycolysis Fatigue rate: increases from 1 to 2B
54
Intracellular and extracellular concentration of Na, K, Ca, Cl
Na- 12, 145 K- 155, 4.5 Cl- 4.2, 116 Ca- 0.0001, 1