Calcium Homeostasis - Part 2
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Questions and Answers

What is the approximate extracellular concentration of Ca2+ in mM?

  • 1 mM (correct)
  • 0.1 mM
  • 0.5 mM
  • 10 mM

Which protein is not classified as a calcium binding protein?

  • Calmodulin
  • S100 proteins
  • Calsquestrin
  • Protein kinase C (correct)

Which of the following is a mechanism for calcium influx into cells?

  • Ca2+ ATPases
  • Voltage-gated Ca2+ channels (correct)
  • Calnexin
  • Calmodulin

How many calcium binding sites does Calsquestrin have?

<p>70 (A)</p> Signup and view all the answers

What type of ATPase is the Sarcoplasmic reticulum Ca2+ ATPase (SERCA)?

<p>P-Type ATPase (D)</p> Signup and view all the answers

What distinguishes the Plasma membrane Ca2+ ATPase (PMCA) from SERCA?

<p>PMCA transfers H+ ions in a 1:1 ratio (B)</p> Signup and view all the answers

Which ion exchanger is involved in the removal of Ca2+ from cells?

<p>Na+/Ca2+ exchanger (D)</p> Signup and view all the answers

What is the primary role of calcium buffering proteins?

<p>To maintain calcium homeostasis (B)</p> Signup and view all the answers

Which of the following is a characteristic of Ca2+-ATPases?

<p>They are part of the P-Type family of ATPases (C)</p> Signup and view all the answers

Which calcium transporter is primarily found in the endoplasmic or sarcoplasmic reticulum?

<p>SERCA (C)</p> Signup and view all the answers

What role do Ca2+ -ATPases play in cellular function?

<p>They help maintain basal Ca2+ levels. (B)</p> Signup and view all the answers

What is the function of sodium/calcium exchangers in cells?

<p>To extrude calcium ions in exchange for sodium ions. (B)</p> Signup and view all the answers

Which types of proteins can buffer free Ca2+ in cells?

<p>Calmodulin and troponin. (C)</p> Signup and view all the answers

What is the primary effect of GPCR activation in calcium signalling?

<p>Producing IP3 and DAG to stimulate Ca2+ release. (D)</p> Signup and view all the answers

Which receptors are specifically associated with membrane calcium flow?

<p>STIM and Orai receptors. (C)</p> Signup and view all the answers

How does calcium contribute to neurotransmitter release?

<p>By promoting the fusion of vesicles with the cell membrane. (B)</p> Signup and view all the answers

Which process is NOT directly influenced by intracellular calcium signaling?

<p>Gene transcription. (B)</p> Signup and view all the answers

What is the primary function of PMCA in cellular calcium regulation?

<p>Moves 1 Ca2+ out of the cell for each ATP hydrolyzed (A)</p> Signup and view all the answers

What physiological process requires calcium's role in synaptic plasticity?

<p>Long-term potentiation. (D)</p> Signup and view all the answers

Which proteins regulate the activity of SERCA?

<p>Phospholamban and ATP (D)</p> Signup and view all the answers

Which experimental finding highlighted the role of calcium in muscle function?

<p>Omission of calcium prevented muscle contraction. (C)</p> Signup and view all the answers

What ion ratio does the NCX exchanger maintain?

<p>3:1 Na+ and Ca2+ (C)</p> Signup and view all the answers

Which cellular function is primarily affected by calcium-dependent conductance?

<p>Transmission of nerve impulses. (C)</p> Signup and view all the answers

Which CA2+ channel subtypes correspond to the nervous system?

<p>Cav2 and Cav3 (C)</p> Signup and view all the answers

What is the primary role of the alpha1 subunit in voltage-gated Ca2+ channels?

<p>Contains ion selective residues and voltage sensor (D)</p> Signup and view all the answers

How does inositol 1,4,5-trisphosphate (IP3) facilitate Ca2+ release?

<p>By triggering IP3 receptors on the ER membrane (C)</p> Signup and view all the answers

What determines the calcium affinity states of SERCA?

<p>The E1 and E2 conformations (C)</p> Signup and view all the answers

From which genes are the voltage-gated Ca2+ channels α1 subunits encoded?

<p>CACNA1 (C)</p> Signup and view all the answers

What is the effect of calmodulin on the PMCA activity?

<p>Increases the activity (B)</p> Signup and view all the answers

How many splice variants are produced by the ATP2B genes for PMCA?

<p>4 (A)</p> Signup and view all the answers

What is the primary function of STIM1 proteins in store-operated calcium entry (SOCE)?

<p>To sense ER luminal Ca2+ levels (D)</p> Signup and view all the answers

Which two proteins are primarily involved in store-operated calcium entry?

<p>STIM1 and Orai1 (C)</p> Signup and view all the answers

What occurs to STIM1 proteins upon calcium store-depletion?

<p>They undergo oligomerization and translocation (A)</p> Signup and view all the answers

How does store-operated calcium entry affect cytosolic Ca2+ levels during prolonged cellular processes?

<p>It allows for more prolonged increases in cytosolic Ca2+ (D)</p> Signup and view all the answers

What is the role of calcium-binding proteins in the intracellular calcium homeostasis?

<p>They bind and buffer intracellular calcium concentration (C)</p> Signup and view all the answers

What is a characteristic of Ca2+ ATPases involved in calcium transport?

<p>They function at different cellular locations like plasma membrane and organelles (B)</p> Signup and view all the answers

What mutation effect is associated with individuals who have gain-of-function mutations in STIM1?

<p>Increased SOCE activity (C)</p> Signup and view all the answers

What types of channels are activated as a result of STIM1 translocation?

<p>Store-operated calcium channels (D)</p> Signup and view all the answers

Which cellular organelle is primarily responsible for binding intracellular calcium?

<p>Endoplasmic reticulum (D)</p> Signup and view all the answers

Flashcards

Calcium Homeostasis

The process of maintaining a stable level of calcium ions (Ca2+) inside cells.

Ca2+-ATPases

Proteins that pump calcium ions out of cells, maintaining low intracellular calcium.

Na+/Ca2+ Exchangers

Proteins that move sodium ions into and calcium ions out of cells.

Intracellular Calcium Buffering

Processes that maintain a low, free calcium concentration in the cytoplasm.

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Voltage-Gated Calcium Channels

Channels that open and allow calcium entry in response to changes in membrane voltage.

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IP3 and DAG

Signaling molecules produced by G-protein-coupled receptors (GPCRs) that trigger calcium release.

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STIM and Orai

Proteins involved in calcium release from intracellular stores and entry into the cytosol.

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Exocytosis

Release of substances from a cell.

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Muscle Contraction

Calcium plays a major role in triggering muscle contraction.

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Neurotransmission

Transmission of signals between nerve cells.

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Calcium Homeostasis

The process that maintains a very precise calcium concentration within cells despite its fluctuations outside.

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Calcium Transporters

Specialized proteins that move calcium ions into and out of cells and organelles.

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Extracellular Ca2+

Calcium ions present outside of cells.

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Cytoplasmic Ca2+

Calcium ions inside the cell's cytoplasm.

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Ca2+ ATPases

Essential pumps that use ATP to move calcium across membranes.

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Plasma Membrane Ca2+ ATPase (PMCA)

A type of Ca2+ ATPase located in the cell membrane facilitating calcium removal from the cytosol.

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Sarcoplasmic Reticulum Ca2+ ATPase (SERCA)

A type of Ca2+ ATPase primarily found in the sarcoplasmic reticulum responsible for calcium uptake by storing it within the organelle.

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Voltage-gated Ca2+ channels

Channels that open and close in response to changes in membrane potential, allowing calcium to enter cells.

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Calcium Buffering Proteins

Proteins that bind calcium to prevent it from reaching high concentrations or causing unwanted effects.

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EF-hand motif

A recurring structural motif found in proteins, particularly those involved in calcium binding.

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PMCA

Plasma membrane Ca2+-ATPase; pumps calcium out of the cell, using ATP.

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SERCA

Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase; pumps calcium into the sarcoplasmic/endoplasmic reticulum, using ATP.

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NCX

Sodium-Calcium Exchanger; moves calcium out of, and sodium into the cell.

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VGCC

Voltage-gated Calcium Channels; open and close in response to changes in membrane potential, allowing calcium to flow in.

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IP3

Inositol 1,4,5-trisphosphate; a second messenger that triggers calcium release from internal stores.

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Ca2+-ATPase

An enzyme that uses energy from ATP to move calcium ions across membranes.

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Subunits of Voltage-gated Ca2+ channels

Channels consist of alpha1, beta, alpha2delta, and gamma subunits.

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L-type Ca2+ Channels

A type of voltage-gated calcium channel widespread throughout many cells, including cardiac, smooth, and skeletal muscle.

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Calcium concentration in E1 state

high calcium affinity (μM)

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Calcium concentration in E2 state

low calcium affinity (mM)

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IP3R structure

IP3R are tetramers of four transmembrane helices.

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SOCE

Store-operated calcium entry; a process that allows prolonged increases in cytosolic calcium.

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STIM proteins

Single-pass transmembrane proteins that detect ER luminal Ca2+ levels.

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Orai proteins

Proteins that form channels in the plasma membrane, allowing calcium entry.

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STIM1 oligomerization

When calcium stores decrease, STIM1 proteins clump together.

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Puncta formation

STIM1 proteins cluster on the ER/SR and plasma membrane.

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Calcium ATPases

Proteins that pump calcium ions out of cells or into organelles.

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ER calcium stores

Cellular compartments with calcium bound to proteins.

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Gain-of-function STIM1 mutations

Mutations that cause increased SOCE activity.

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Intracellular calcium homeostasis

Maintaining a stable level of calcium inside the cell.

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Study Notes

Calcium Homeostasis - Part 2

  • Calcium homeostasis is maintained both extracellularly and intracellularly
  • Intracellular calcium is primarily bound by calcium-binding proteins or calcium-buffering proteins in the cytoplasm and organelles
  • Calcium entry and exit from cells and organelles is facilitated by various proteins

Calcium Entry Mechanisms

  • Ca2+-ATPases
    • ATP2B (plasma membrane), ATP2A (endoplasmic/sarcoplasmic reticulum), ATP2C (golgi)
  • Voltage-gated Ca2+ channels
    • L-type calcium channels
  • Na+/Ca2+ exchanger
    • NCX1, NCX2 and NCX3
  • Permeability transition pore

Calcium Binding Proteins

  • EF-hand motif containing proteins
    • Calmodulin
    • S100 proteins
    • Calcineurin
  • C2-domain containing proteins
    • Protein kinase C (PKC)
    • Phospholipase-A (PLA)
    • Phospholipase-C (PLC)

Calcium Buffering proteins

  • Calnexin
    • Endoplasmic reticulum
    • 25 calcium binding sites
  • Calsquestrin
    • Sarcoplasmic reticulum
    • 70 calcium binding sites

Inositol 1,4,5-trisphosphate (IP3)

  • Ca2+ release from intracellular stores (e.g., endoplasmic reticulum) is triggered by IP3
  • IP3 receptors (IP3R) are located on the membranes of intracellular stores
  • IP3 receptors are 4 transmembrane spanning helices

Voltage-gated Ca2+ Channels (VGCC/VOC)

  • The α subunit is the largest and contains the voltage-sensor, calcium-selective residues (e.g., glutamine)
  • The β subunit, is intracellular
  • The α2β subunit is extracellular (two proteins bound by disulfide bridges)
  • These channels are encoded by the CACNA1 genes
  • Three subfamilies
    • L-type channels
    • P/Q-type channels
    • N-type channels
    • R-type channels
    • T-type channels

Store-Operated Calcium Entry (SOCE)

  • Intracellular Ca2+ stores are limited.
  • SOCE is a long-lasting influx mechanism triggered by store depletion
  • It is involved to prolonged elevation of cytosolic Ca2+ (e.g. transcription)
  • Two key proteins are involved: STIM1 and Orai
  • SOCE involves STIM1 protein oligomerization and translocation to the ER/SR-PM (forming puncta), binding to the same Orai site, and channel activation which allows Ca2+ entry.

Ca2+-ATPases - PMCA

  • PMCA, pumps 1 Ca2+ out of the cell for each ATP hydrolyzed.
  • Activity can be increased by binding of calmodulin to the c-terminal domain.
  • Encoded by 4 genes (ATP2B1-4) and results in 4 splice variants (PMCA1-4).

Ca2+-ATPases - SERCA

  • SERCA pumps 2 Ca2+ into the sarcoplasmic reticulum.
  • Activity can be regulated by ATP and phospholamban (PLN).
  • Encoded by 3 genes (ATP2A1-3) with variants

NCX (Sodium/Calcium Exchanger)

  • NCX belongs to the Ca2+, cation antiporter superfamily;
  • This exchanger moves Ca2+ out and Na+ in or out from the cell depending on electrochemical gradients
  • 3:1 Na+ and Ca2+ exchange is possible

Metabloites of Vitamin D and 25-Hydroxyvitamin D

  • NCX belongs to the superfamily of Ca2+, cation antiporter
  • Moves Ca2+ out of cells
  • Activity of Na+ & Ca2+ exchanger can be changes based on calcium-binding domains (CBD)
  • Encoded by the SLC8 gene and produces 3 isoforms (NCX1, NCX2 and NCX3) which are found in muscle and brain

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Calcium Homeostasis Part 2 PDF

Description

Explore the intricate mechanisms involved in calcium homeostasis, focusing on both extracellular and intracellular regulation. This quiz covers crucial calcium entry mechanisms, binding proteins, and buffering systems essential for cell function. Test your understanding of these vital biological processes.

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