Smooth Myocytes

Question 1

what is smooth muscle contraction dependent on?

Answer 1

Ca2+ from extracellular material as SR is rudimentary and cannot store sufficient Ca2+ for contraction

upon depol, Ca2+ enters cell

Question 2

how is Ca2+ used in smooth muscle to cause contraction?

Answer 2

4 Ca2+ bind to calmodulin molecule, forming Ca-calmodulin complex
facilitates phosphorylation of myosin regulatory light chain kinase (MLCK)

1 Ca-C complex can initiate cross bridge cycle at multiple sites: significantly less Ca2+ needed for smooth muscle contraction than skeletal

Question 3

how is contraction initiated in smooth muscle?

Answer 3

has slow waves caused by gradual Ca2+ influx that can reach threshold to initiate contraction
e.g. in interstitial cell of Cajal in SI

rate of depol influenced by NTs from varicosities

Question 4

what effect to NTs have on rate of smooth muscle depol?

Answer 4

ACh from parasymp: bind to muscarinic and trigger phosphorylation cascade to increase Ca2+ influx: increases rate of depol

NA from symp: bind to adrenergic and decrease rate of Ca2+ influx, slower rate of depol

Question 5

how does smooth muscle relax?

Answer 5

removal of Ca2+ does not cause immediate relaxation

removed through similar mechs to skeletal e.g. NCX/PMCA (NKA assisted) but MLCK still phosphorylated and continues cross bridge cycling

can maintain tonic contraction while skeletal muscle would fatigue

to relax: phosphatase enzymes cleave Pi from myosin group, halting cross-bridge cycle

Question 6

what can modulate the action of the interstitial cells of Cajal?

Answer 6

cAMP initiates depolarisation through PKA activation

cAMP activates PKA, removing reg subunits from tetrameric holoenzyme

phosphorylates PLC, which phosphs inositol 1,4,5 phosphate receptors, opening IP3-gated Ca2+ release channel on SR

mediates Ca2+ efflux that underlies slow wave propagation: allows smooth muscle contraction

Question 7

what is the effect of cAMP in smooth muscle cells? how does it accomplish this?

Answer 7

leads to relaxation

high intracellular cAMP activates ++ PKA

PKA inhibits MLCK by phosphorylation, prevents Ca-Calmod complex from binding it, prevents cross bridge cycling = relaxation

also phosphorylates SERCA Ca ATPase, pumps Ca2+ into SR = decreased intracell cAMP = relaxation