Lecture 13 Part 2 Flashcards
What can contractile stimulation of smooth muscle occur by?
Receptor stimulation, mechanical perturbation and electrical excitation
What can receptor stimulation occur by?
Neuronal (noradrenaline), hormonal (Adrenaline, angiotensin 2) and Paracrine (adenosine, histamine)
What is mechanical perturbation?
Stretch, intraluminal pressure
What is electrical excitation?
Action potential generation (uncommon in vascular smooth muscle)
What is the role for ca2+ in smooth muscle contraction?
Free ca2+ regulates contraction of membrane permeabilised smooth muscle
What are the mechanisms to increase cytosolic ca2+?
Ca2+ release from intracellular organelles from the SR and ca2+ entry into the cell through plasma lemma channels
How is ca2+ released from the SR?
IP3 induced ca2+ release from the SR mediated by IP3 and CICR release mediated from RYR receptors
What is the contractile mechanism in the cardiac muscles?
Increase in cytosolic ca2+,
Binding of ca2+ to calmodulin,
Calmodulin complex is formed,
Activates myosin light chain kinase (MLCK)
Causes phosphorylation of MYCL20
Activates contractions
How can you cause relaxation in smooth muscle?
You have a light chain phosphatase which can dephosphorylate the MLC20 subunit which causes relaxation
What does a global increase in ca2+ lead to?
Leads to a change in vascular diameters which leads to vasoconstriction
What can be used to measure pressurised arteries to measure ca2+?
Laser scanning confocal microscopy
What is a phenylephrine induced tonic contraction?
Upon contractile stimulation another form of ca2+ dynamics occurs individual cell dynamics
What would happen if all of the cells had the same increase?
Get an increase, decrease cause of contraction
What is change in ca2+ proportional to?
Intensity of the stimuli
What are smooth muscles cells ca2+ not?
They are not unidirectional
What are smooth muscle cells ca2+ waves?
They are asynchronous
What is good about asynchronous ca2+ waves?
They are more likely to be advantageous for maintaining constant tone
What are ca2+ changes in arterial smooth muscle like?
They are dynamic and spatially regulated
What can ca2+ sparks regulate?
The electrical excitability of vascular smooth muscle cells
What does a spontaneous transient inward current =
Depolarisation
What does a spontaneous transient outward current =
Hyperpolarisation
What do ca2+ sparks generally act as?
A brake for tone development, they are more frequent when tone is present
What is important for SR?
Its location it’s important, it needs to be close to the mitochondria and filaments, as well as caveolae
Does physical disruption of plasma lemma caveolae alter ca2+ dynamics?
Yes, cholesterol sequestion using methyl B cyclodextrin can distrupt the calveolae
What does extrinsic treatment reduce?
Reduces calveolae in vascular smooth muscle cells
What does dextrin treatment also reduce?
The number of ca2+ waves in vascular smooth muscle cells
What happens after disruption of caveolae?
Reduced frequency and amplitude of ca2+ sparks in smooth muscle cells
What does release of ca2+ from RYR receptors trigger?
STOCs and STICs and they need myogenic or agonist stimulated tone present for ca2+ sparks
Where do ca2+ waves originate?
At one end of the smooth muscle cell - the propagate by peripheral and central localisation of the SR
When do ca2+ waves occur?
During myogenic or agonist stimulated tone
What is ca2+ sensitisation like in vascular smooth muscle cells?
Greater force of contraction in response to noradrenaline compared with KCL but with same ca2+
What is noradrenaline induced vasoconstriction?
Alpha 1 receptor stimulation, ca2+ release from SR by IP3 receptors, PKC inhibition of MYLCP via CPI-17