6.2 calcium sigaling Flashcards
(26 cards)
Q: What is the endothelium?
A: It is the single and innermost layer of a blood vessel.
Q: What is the luminal side of the endothelium exposed to?
A: Mediators and mechanical forces from the bloodstream.
Q: What is the abluminal side of the endothelium?
A: It projects from endothelial cells to contact vascular smooth muscle cells (VSMC).
Q: What are myoendothelial projections (MEPs)?
A: Tiny projections from endothelial cells through the internal elastic lamina to VSMCs that allow communication.
Q: What is required for Ach-induced vasodilation?
A: Functional endothelium and endothelial nitric oxide synthase (eNOS) activation.
Q: What activates eNOS?
A: GPCR activation increases mobilisation of intracellular Ca²⁺ stores, leading to eNOS activation and increased NO production.
Q: How does calcium activate eNOS?
A: Via Ca²⁺/Calmodulin (CaM) complex which promotes eNOS phosphorylation and activity.
Q: What does the CaM-eNOS interaction require?
A: Binding of CaM with 4 Ca²⁺ ions causes a conformational change that allows eNOS activation through phosphorylation at Ser1177.
Q: What stabilizes active eNOS?
A: Release from caveolin-1, which supports electron flow for converting L-arginine to NO.
Q: What is EDH and its role in vasodilation?
A: Endothelium-derived hyperpolarisation (EDH) contributes to vasodilation, especially in small arteries.
Q: What happens during EDH-mediated vasodilation?
A: Ca²⁺ increase activates SK and IK K⁺ channels, K⁺ efflux hyperpolarises the EC membrane, spreading to VSMCs, reducing L-type channel activity and promoting dilation.
Q: In which vessels is NO’s vasodilation effect less dominant?
A: Small diameter arteries, like mesenteric or cerebral arteries.
Q: What is the size of a myoendothelial projection (MEP)?
A: Approximately 0.5 µm in width and depth.
Q: What connexins are present at MEP gap junctions?
A: Cx37, Cx40, Cx43, and Cx45.
Q: Where are MEPs mostly located?
A: In small resistance arteries and arterioles.
Q: What signaling molecules pass from EC to VSMC via MEPs?
A: NO and EDH (hyperpolarisation).
Q: What signaling molecules pass from VSMC to EC via MEPs?
A: IP3 and Ca²⁺.
Q: How does phenylephrine affect vascular tone?
A: Binds to α1 receptors on VSMC, increasing DAG and IP3, leading to Ca²⁺ influx and vasoconstriction.
Q: How does IP3 affect endothelial cells?
A: It binds IP3 receptors on the ER to release Ca²⁺ stores and opens TRPV4 channels for further Ca²⁺ influx.
Q: What does increased endothelial Ca²⁺ activate?
A: IK and SK channels, causing hyperpolarisation and relaxation (negative feedback to control tone).
Q: What causes flow-induced vasodilation?
A: Shear stress activates P2X, PIEZO1, TRPP1, and TRPV4 channels, increasing intracellular Ca²⁺ in ECs.
Q: What are the outcomes of flow-induced vasodilation?
A: Activation of eNOS and NO production, and activation of IK/SK channels for EDH-mediated vasodilation.
Q: What are the mechanisms of abnormal calcium signaling in hypertension?
A: Enhanced VSMC excitability, impaired endothelial function, and altered calcium-handling proteins.
Q: How does enhanced VSMC excitability contribute to hypertension?
A: Overactive L-type Ca²⁺ channels increase Ca²⁺ influx, raising intracellular concentration and blood pressure.
