Unit 11: smooth muscle & cardiac muscle Flashcards
why is smooth muscle considered more efficient than skeletal muscle?
- 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
list out how smooth muscle is structurally different than skeletal muscle
- 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
(3) ways Ca2+ gets into smooth muscle cells
- Ca2+ leak channels
- VG Ca2+ channels
- ligand gated ion channels
why would a patient with hypocalcemia have a lower blood pressure
- vascular smooth muscle cells have less developed SRs and are dependent on outside Ca2+ to contract > no vascular tone > no BP
what are the (2) types of smooth mucle
- visceral smooth muscle*
- multi-unit smooth muscle
*AKA “unitary” smooth muscle
- 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+)
VISCERAL smooth muscle
AKA unitary smooth muscle
- 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
MULTI-UNIT smooth muscle
this organ is made of both smooth and skeletal muscle
esophagus
list out the (3) layers to vascular smooth muscle cells and their alternate names
- adventitia = tunica adventitia/externa (outermost layer)
- smooth muscle lining = tunica media (middle layer)
- endothelium = tunica intima (innermost layer)
what is the function of the adventitia of the VSMC
structural support
these are the only vessels that don’t have a smooth muscle layer WITH endothelium
these vessels ONLY HAVE endothelium
the capillaries
these two layers communicate with each other in VSMC
tunica media
tunica intima
via NTs & gasses (NO)
describe how myosin in smooth muscle is structurally different than myosin in skeletal muscle
- 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
delineate the pathway for smooth muscle to contract
- ICF Ca2+ [ ] increases when Ca2+ enters the cell through Ca2+ channels in the cell membrane or through the SR (external Ca2+»_space; SR Ca2+)
Can happen via:
* leak Ca2+ channels
* VG Ca2+ channels (L-type: slow opening & stays open longer)
* ligand gated Ca2+ ion channels - Calmodulin (a protein in smooth muscle) binds to Ca2+ and wraps itself around inactive regulatory myosin light chains to become a calmodulin complex
- calmodulin complex has a conformation change and will become active myosin light chain kinase
- MLCK phosphorylates inactive myosin and myosin now becomes active
- active myosin can now contract the smooth muscle
list the different ways smooth muscle cells can halt contraction
- 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
what activates protein kinase G in VSMCs?
cyclic GMP
what is protein kinase G’s (PKG) role in vascular smooth muscle cells?
- phosphorylates MLCK
- 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
how do endothelial cells play a role in causing VSMCs to relax?
- ACh or bradykinin binds to a m-ACh-R cell in the endothelial cell
- Ca2+ is released from endoplasmic reticulum in endothelial cell
- Ca2+ binds to calmodulin > calmodulin complex undergoes conformation change to increase eNOS activity in endothelial cell
- eNOS acts on arginine to produce nitric oxide (NO)
- NO diffuses across the endothelial cell to neighboring VSMC
- NO, now in the VSMC, interacts with soluble guanylyl cyclase to turn GTP into cGMP
- 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
what is phosphodiesterase’s (PDE) role in the VSMC?
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
name the PDE-i mentioned in class
sildenafil
what is another pathway that allows VSMCs to contract?
the Gq GPCR pathway via alpha 1 agonism
delineate the pathway of alpha-1 agonists to cause VSMCs to contract
- alpha-1 agonist binds to alpha-1-R
- Gq GPCR is activated; the alpha-q subunit migrates to interact with phospholipase C (PLC)
- PLC cleaves DAG from ptdlns 4, 5P2 inside the cell membrane
- as a result DAG causes PKC to become activated > inhibits MLCP activity > creates more active myosin > VSMC contraction
- PLC increases inositoltriphosphate (IP3) activity to increase > increases Ca2+ levels > calmodulin + Ca2+ binding > conformnation change > increasing MLCK activity > activates myosin > VSMC contraction
how does serotonin (5HT) cause vasoconstriction in VSMCs?
5HT follows the Gq pathway
true or false: Ca2+ is not necessary to have the smooth muscle contract
true (it helps, but is not necessary – can contract via other pathways)
APs are ALSO NOT NECESSARY for contraction
for one cardiac cycle, about what percent of the Ca2+ that gets used comes from the SR? from outside the cardiac myocyte?
80% from SR
20% from outside
what types of Ca2+ channels are found on the cardiac myocyte?
- 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
what is the T-tubules role in the cardiac myocyte?
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
20% of the Ca2+ used in a cardiac AP gets influxed via Ca2+ ion channels; ___ % of Ca2+ gets effluxed via these same Ca2+ channels
20
& 80% gets placed back into the SR
what is calsequestrin?
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+
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
phospholamban
what would inhibiting phospholamban with drugs do?
increases activity of SERCA pump > **shortens the contraction ** > cell resets quicker > may increase HR
which two receptors antagonize each other’s activity on the cardiac myocyte
beta (adrenergic) & m-ACh-R (cholinergic)
