[WG21:Chp3 - visceral smooth muscles]
Binding of acetylcholine to muscarinic receptors
--> Increased Ca2+ influx
* Primarily from ECF via voltage-gated and ligand-gated Ca2+ channels
* Predominantly ligand-gated Ca2+ channels in the sarcolemma
--> Ca2+ binds to calmodulin
--> Ca2-calmodulin complex activates calmodulin-dependent myosin light chain kinase (MLCK)
--> MLCK catalyze phosphorylation of myosin light chain
--> Myosin light chain activated
--> Actin slides on myosin
--> Contraction
NB:
Myosin is dephosphorylated by myosin light chain phosphatase
--> Relaxation does not necessarily occur
Other mechanisms are involved in relaxation
NB:
Myosin light chain phosphatase is inhibited when phosphorylated, and activated when dephosphorylated
Myosin cross-bridge remain attached to actin after cytoplasmic [Ca2+] falls
--> Contraction is often tonic
In Ganong, it seems to be suggesting vascular smooth muscles and visceral smooth muscles are slightly different.
Also that SR plays an important role in relaxation.
Thus,
Ca2+ influx from ECF via voltage-gated Ca2+ channels
--> Diffuse increase in intracellular [Ca2+]
--> Contraction initiated
However,
Ca2+ influx also triggers Ca2+ release from SR via ryanodine receptors
--> High local [Ca2+]
--> Activates Ca2+-activated K+ channels (Big K or BK)
--> Increase K+ efflux via BK channels
--> Increase Vm
--> Voltage-gated Ca2+ channel closed
--> Relaxation
In Berne and Levy, it seems to be suggesting that:
Thus, the sequence of events is:
Agonist activates a receptor in the vascular smooth muscle membrane
--> Activation of phospholipase C via Gq-protein
--> PIP2 --> DAG + IP3
--> IP3 causes release of Ca2+ from SR
--> Contraction via Calmodulin, MLCK, etc
Relaxation is by reduction of [Ca2+]
[WG21: p84-85]
Vm more negative
--> Decrease spike frequency
--> Relaxation
Stimulation of beta-adrenergic
--> Increased cAMP (probably due to increased intracellular [Ca2+] binding)
--> Inhibition of MLCK
--> Relaxation
Stimulation of alpha-adrenergic
--> Increased Ca2+ efflux (how????)
--> Contraction inhibited
Vm less negative
--> Increase phospholipase C and IP3
--> Increased intracellular [Ca2+]
--> Spikes more frequent
--> Increased tonic tension and rhythmic contraction
NB: