Smooth muscle innervation Flashcards
What is the rough Em of smooth muscle cells?
-50mV
Compare APs in smooth and skeletal muscle
Smooth - Slower upstroke and last longer
What current drives depol in SMC?
L Ca2+ current
What repolarises smooth muscle cells?
Ca2+ activated K+ channel and VGKC
Why is SM nerve transmission described as “en passant”
APs pass along neurone across each varicosity releasing neurotransmitter into synaptic cleft
How is visceral SM similar to SAN?
Can exhibit pacemaker activity
Describe what triggers contraction in single unit SM?
Pacemaker cells - spontaneous contraction.
Modified by ANS and neurotransmitters etc
Describe what triggers activation of multiunit SM?
Motor neurones (contraction initiated by neurotransmitter)
True of false, VGNC drives SM action potential?
False, it’s Ca2+ (L type)
How do SM open SR (what mechanism)?
Intracellular signals, i.e. secondary messenger system
What are 3 mechanism for Ca2+ increase in SM?
Ligand gated ion channel
Ca2+ via L type channel (NA = agonist and depolarise cell membrane)
IP3 mediated Ca2+ release from SR
Instead of troponin, what initiates contraction in SM?
Myosin phosphorylated which activates its ATPase ability
Does SM need changes in Em for contraction?
No
What does tropomyosin do at rest?
Blocks myosin binding site, stabilises actin
What is functionally similar to troponin?
Caldesmon - regulates position of tropomyosin
Describe structure of myosin
2 heavy chains, 4 light chains head, hinge and tail region
Which part of myosin forms cross bridge with actin?
Head
What part of myosin has ATPase activity?
Head
In absence of Ca2+ what prevent actin myosin binding?
Myosin light chain (not tropomyosin)
True or false, tropomyosin stops actin myosin binding when Ca2+ absent (SM)?
False, it’s Myosin light chain
How many Ca2+ bind to calmodulin?
4
What does Ca2+ bind to?
Calmodulin
What 3 things does CalCam act on, what are the effects?
Activates MLCK - MLCK phosphorlylates P light chain of myosin (MLC)
CalCam acts on caldesmon removes inhibition of tropomyosin
Calcam binds to calponin -removes inhibiton on myosin head ATPase activity
Which part of myosin regulates cross bridge cycling?
P light chain
What happens after MLC phosphorylated?
Relieves MLC inhibition and ATP hydrolysed by myosin head and cross bridge cycling occurs
What happens in relaxation?
Dephos of MLC by MLCP when Ca2+ falls
What are the roles of PKA and PKG in smooth muscle relaxation on MLCK?
Phophorylate MLCK (inactive)
Reduce Ca2+ sensitivity of MLCK - more calcium calmodulin needed to activate it
Promote relaxation
How do PKA and PKG promote relaxation?
Phosphorylate/desensitise MLCK
Phosphorylate K+ channel to hyperpolarise membrane inhibits Ca2+ entry
What are the roles of calponin and caldesmon (how do they compare to troponin/tropomyosin)?
Caldesmon (tropomyosin) and calponin (inhibits heads ATPase activity)
What does DAG subunit do to release Ca2+/promote contraction?
DAG, along with Ca2+, activates protein kinase C (PKC) which promotes contraction/Ca2+ entry
What does PKC do?
Phosphorylates L-type Ca2+ channels
Phosphorylates MLCP (inhibits it)
What inhibits MLCP?
PKC
What is the effect of decreasing Ca2+ in SM contraction?
Inactivates MLCK
What does Rhokinase do?
Inhibit MLCP (increased sensitization)
What is meant by SM being in latch state?
Uncoupling of actin and myosin slow - latch process. (after MLC dephos)
What is the benefit of latch mechanism?
Tension generated for longer period (sustained contraction) at low energy cost and at low Ca2+
How does para and symp promote contraction (neurotransmitter and receptor)?
Para: Ach: M3
Symp: NA: alpha 1
How can symp system inhibit SM contraction?
NA on beta 2
Which cells secrete NO?
Endothelial cells
What GPCR is stimulated, and by what in the NO synthesis pathway?
M3 by ACh
Pathway for NO production
ACh - M3 - Ca2+ calmodulin, activate eNOS - L arginine to L citrulline - release NO
What does NO do after being made in endothelial cells (give pathway)?
NO diffuse to tunica media in SMC
Stimualte cGMP, activate PKG,
What activates MLCK?
Calcium-calmodulin complex
What generates acetylcholine-induced contraction of ileal smooth muscle?
IP3 increase
What generates isoprenaline-induced relaxation of bronchial smooth muscle?
cAMP increase
How does raised cAMP (bronchiolar smooth muscle) cause relaxation?
cAMP relaxes bronchiolar smooth muscle phosphorylating myosin light chain kinase.
Does smooth muscle have gap junctions?
Yes
