Unit 11: smooth muscle & cardiac muscle

Question 1

why is smooth muscle considered more efficient than skeletal muscle?

Answer 1

• cross bridge cycling is slower
  + the smooth muscle myosin heads get released slower from actin; this can maintain the force of contraction longer
  + uses a “latch mechanism” which means the smooth muscle uses a small amount of energy to produce a longer lasting force of contraction by “latching” on to the actin for a much longer time
• smooth muscle is stronger on a per gram basis – skeletal muscle can produce more FORCE but the muscles are much LARGER

Question 2

list out how smooth muscle is structurally different than skeletal muscle

Answer 2

• contains dense bodies – these anchor actin filaments in smooth muscle (the “z-disc” equivalent in smooth muscle)
• smooth muscle cells are much smaller than skeletal muscle cells
• connect to each other via gap junctions embedded in cell walls
• actin:myosin ratio is much larger in smooth muscle compared to skeletal muscle (10-20:1 smooth; 2:1 skeletal)
• smooth muscle SRs contain less Ca2+ than skeletal muscle d/t having less developed SRs

Question 3

(3) ways Ca2+ gets into smooth muscle cells

Answer 3

1. Ca2+ leak channels
2. VG Ca2+ channels
3. ligand gated ion channels

Question 4

why would a patient with hypocalcemia have a lower blood pressure

Answer 4

• vascular smooth muscle cells have less developed SRs and are dependent on outside Ca2+ to contract > no vascular tone > no BP

Question 5

what are the (2) types of smooth mucle

Answer 5

1. visceral smooth muscle*
2. multi-unit smooth muscle

*AKA “unitary” smooth muscle

Question 6

• the majority type of smooth muscle
• intestinal smooth muscle
• vascular smooth muscle
• this type of smooth muscle allows ions to flow through gap junctions (Na+/Ca2+)

Answer 6

VISCERAL smooth muscle
AKA unitary smooth muscle

Question 7

• this type of smooth muscle is dependent on NTs
• produces relatively smaller APs with this type of smooth muscle
• ciliary/IRIS muscles in the eye use this type of smooth muscle
• autonomic neuron varicosity

Answer 7

MULTI-UNIT smooth muscle

Question 8

this organ is made of both smooth and skeletal muscle

Answer 8

esophagus

Question 9

list out the (3) layers to vascular smooth muscle cells and their alternate names

Answer 9

1. adventitia = tunica adventitia/externa (outermost layer)
2. smooth muscle lining = tunica media (middle layer)
3. endothelium = tunica intima (innermost layer)

Question 10

what is the function of the adventitia of the VSMC

Answer 10

structural support

Question 11

these are the only vessels that don’t have a smooth muscle layer WITH endothelium

these vessels ONLY HAVE endothelium

Answer 11

the capillaries

Question 12

these two layers communicate with each other in VSMC

Answer 12

tunica media
tunica intima

via NTs & gasses (NO)

Question 13

describe how myosin in smooth muscle is structurally different than myosin in skeletal muscle

Answer 13

• there is no m-line in smooth muscle cells
• there are dense bodies instead of “z-discs” in smooth muscles
• the myosin molecular arrangement is different in smooth muscle in that it allows the smooth muscle to shorten much more than skeletal muscle; this allows much more force to be generated during smooth muscle contraction

Question 14

delineate the pathway for smooth muscle to contract

Answer 14

1. ICF Ca2+ [ ] increases when Ca2+ enters the cell through Ca2+ channels in the cell membrane or through the SR (external Ca2+&raquo_space; SR Ca2+)
   Can happen via:
   * leak Ca2+ channels
   * VG Ca2+ channels (L-type: slow opening & stays open longer)
   * ligand gated Ca2+ ion channels
2. Calmodulin (a protein in smooth muscle) binds to Ca2+ and wraps itself around inactive regulatory myosin light chains to become a calmodulin complex
3. calmodulin complex has a conformation change and will become active myosin light chain kinase
4. MLCK phosphorylates inactive myosin and myosin now becomes active
5. active myosin can now contract the smooth muscle

Question 15

list the different ways smooth muscle cells can halt contraction

Answer 15

• either active myosin can dephosphorylate with time to become inactive again which will cause the smooth muscle to relax (this is not typically how the body regulates this process)
• myosin phosphatase strips phosphate off of active myosin heads to inactivate myosin; inactive myosin will cause smooth muscle relaxation
• sarcoplasmic Ca2+ can be removed to cause smooth muscle cell relaxation by:
  + the SERCA pump
  + plasma membrane Ca2+ ATPase pumps (PMCA)
  + NCX

Question 16

what activates protein kinase G in VSMCs?

Answer 16

cyclic GMP

Question 17

what is protein kinase G’s (PKG) role in vascular smooth muscle cells?

Answer 17

1. phosphorylates MLCK
2. phosphorylates Ca2+ entry channels

by phosphorylating these structures, it decreases Ca2+ entry into the cell as well as slowing down MLCK activity (to phosphorylate inactive myosin light chains)

therefore, the overall effect will be smooth muscle relaxation

Question 18

how do endothelial cells play a role in causing VSMCs to relax?

Answer 18

1. ACh or bradykinin binds to a m-ACh-R cell in the endothelial cell
2. Ca2+ is released from endoplasmic reticulum in endothelial cell
3. Ca2+ binds to calmodulin > calmodulin complex undergoes conformation change to increase eNOS activity in endothelial cell
4. eNOS acts on arginine to produce nitric oxide (NO)
5. NO diffuses across the endothelial cell to neighboring VSMC
6. NO, now in the VSMC, interacts with soluble guanylyl cyclase to turn GTP into cGMP
7. cGMP upregulates PKG which will decrease Ca2+ influx by phosphorylating the Ca2+ membrane channels as well as decreasing vascular smooth muscle cell contraction by phosphorylating MLCK

Question 19

what is phosphodiesterase’s (PDE) role in the VSMC?

Answer 19

PDE speeds up the process of the inactivation of cGMP

cGMP is unstable at baseline

by PDE speeding up the inactivation of cGMP, PDE essentially will cause the VSMC to contract

Question 20

name the PDE-i mentioned in class

Answer 20

sildenafil

Question 21

what is another pathway that allows VSMCs to contract?

Answer 21

the Gq GPCR pathway via alpha 1 agonism

Question 22

delineate the pathway of alpha-1 agonists to cause VSMCs to contract

Answer 22

1. alpha-1 agonist binds to alpha-1-R
2. Gq GPCR is activated; the alpha-q subunit migrates to interact with phospholipase C (PLC)
3. PLC cleaves DAG from ptdlns 4, 5P2 inside the cell membrane
4. as a result DAG causes PKC to become activated > inhibits MLCP activity > creates more active myosin > VSMC contraction
5. PLC increases inositoltriphosphate (IP3) activity to increase > increases Ca2+ levels > calmodulin + Ca2+ binding > conformnation change > increasing MLCK activity > activates myosin > VSMC contraction

Question 23

how does serotonin (5HT) cause vasoconstriction in VSMCs?

Answer 23

5HT follows the Gq pathway

Question 24

true or false: Ca2+ is not necessary to have the smooth muscle contract

Answer 24

true (it helps, but is not necessary – can contract via other pathways)

APs are ALSO NOT NECESSARY for contraction

Question 25

for one cardiac cycle, about what percent of the Ca2+ that gets used comes from the SR? from outside the cardiac myocyte?

Answer 25

80% from SR 20% from outside

Question 26

what types of Ca2+ channels are found on the cardiac myocyte?

Answer 26

* L-type (slower) * T-type (faster) T-type is faster than L-type and is the initial channel to allow Ca2+ in; L-type is more active in the latter parts of the cardiac AP

Question 27

what is the T-tubules role in the cardiac myocyte?

Answer 27

T-tubules contain a lot of free floating Ca2+ ions -- this is the main resource pool where Ca2+ can get influxed into the cardiac myocyte via T-type and L-type Ca2+ channels

Question 28

20% of the Ca2+ used in a cardiac AP gets influxed via Ca2+ ion channels; ___ % of Ca2+ gets effluxed via these same Ca2+ channels

Answer 28

20 & 80% gets placed back into the SR

Question 29

what is calsequestrin?

Answer 29

calsequestrin is a protein that binds Ca2+ and removes it from solution [ ]; this is especially helpful to the SERCA pump allowing it to work efficienctly in storing more Ca2+ in the SR calsequestrin "sequesters" Ca2+

Question 30

this structure is unique to cardiac myocytes which normally inhibits SERCA pump activity to allow Ca2+ to remain inside the sarcoplasm longer > allows for a longer contraction

Answer 30

phospholamban

Question 31

what would inhibiting phospholamban with drugs do?

Answer 31

increases activity of SERCA pump > **shortens the contraction ** > **cell resets quicker** > may increase HR

Question 32

which two receptors antagonize each other's activity on the cardiac myocyte

Answer 32

beta (adrenergic) & m-ACh-R (cholinergic)