Cole et al 2019 Vasomotion Flashcards
What is vasomotion? What are the 2 key elements? What is vasomotion for?
Rhythmic contraction and relaxation of SMCs
2 key elements are, synchronized activity and oscillatory mechanism for temporal control (entrained by neurons in brain)
Vasomotion is provide blood flow to downstream region for metabolic supply.
What are the molecular underpinnings that support synchronization in vasomotion?
Gap junctions by connexins
How does anesthesia affect vasomotion?
It can either promote or deplete depending on the vessel
Why do we need gap junctions for vasomotion?
To synchronize activities between SMCs through homo or heterocellular connections
Electrical communication between cells
Is synchronization electrical or chemical in nature?
Electrical
Synchronization over long distance is only possible through electrical
What are 3 potential oscillatory mechanisms in vasomotion?
Pacemaker cells, membrane oscillator, cytosolic oscillator
Describe the pathway involved in cytosolic oscillator
GqPCRs (eg. by noradrenaline) can produce IP3s to act on IP3Rs
Ca2+ release from intracellular stores can activate Ca2+ activated Chloride channels -> Causes depolarization
Activate nearby VDCC -> Ca2+ influx to engage crossbridge cycling
Restore intracellular store calcium by SERCA
This cycle creates a rhythm
Are RyRs involved in vasomotion?
Potentially. The effect of RyR depends on where the vessel is from
Activation can block the rhythm (possibly due to ca2+ induced ca2+ release
They are differentially expressed unlike IP3Rs
What are the possible channels involved in vasomotion?
Chloride channels
- bestrophin3 or TMEM16A
- Ca2+ activated
nonselective cation channels
- TRPC3 -> direct PPI with IP3R and activated together
- TRPM4 -> Ca2+ activated
Are endothelial cells involved in vasomotion?
Involvement depends on vessel type
Removing EC from mesenteric artery can block vasomotion
Blocking NO production in cerebral microvessels can enhance vasomotion (but generally NO acts on guanylyl cyclase to produce cGMP and activate chloride channels)
It’s possible role is to facilitate electrical conductance due to longitudinal orientation along vessel
Myoendothelial junctions can allow IP3s to diffuse to endothelial cells and subsequently lead to IK channels to hyperpolarize back through junctions
How is vasomotion entrained in the brain?
They are entrained by interneuron activity in the gamma band
Gamma band oscillation -> 2sec later vasomotion -> 1 sec later increase CBF
Is vasomotion coordinated across hemisphere?
yes, callosal connection is required for coordination
Describe the model of how vasomotion is initiated? Does this happen in vivo or in vitro?
Asynchronouse Ca2+ oscillations detected prior to synchronous elevation and vasomotion
Electrical communication through gap junctions synchronize the oscillations then to initiate vasomotion
This is only detected in vitro and rarely in vivo
Do cells other than SMCs and endothelial cells affect vasomotion?
Yes, astrocytes can amplify or curtail vasomotion through stretch mediated feedback to limit vasomotion
What is a possible mechanism of vasomotion in the brain?
It can be analogous to that of NVC
Neurons can release vasoactive molecules like potassium, which can cause retrograde propagation at a particular frequency -> This was possible optogenetically
Also, recent evidence that vasomotion propagates retrogradely just like sensory stim.
