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Which protein is classified as a calcium binding protein with an EF-hand motif?

  • Calnexin
  • Calcineurin
  • Calmodulin (correct)
  • Calsquestrin
  • What is the primary function of Ca2+-ATPases in muscle contraction?

  • Bind calcium in the cytoplasm
  • Transfer calcium across membranes after contraction (correct)
  • Facilitate calcium influx through voltage-gated channels
  • Act as secondary active transporters
  • Calcium can enter cells through which of the following mechanisms?

  • Osmotic transport
  • Voltage-gated Ca2+ channels (correct)
  • Passive diffusion only
  • Na+/K+ ATPase
  • Which of these statements correctly describes the function of the plasma membrane Ca2+ ATPase (PMCA)?

    <p>It moves Ca2+ out of cells while importing H+.</p> Signup and view all the answers

    Which of the following is NOT a type of calcium transporter mentioned?

    <p>Calmodulin transporters</p> Signup and view all the answers

    Which type of calcium ATPase is responsible for transporting calcium in the sarcoplasmic reticulum?

    <p>SERCA</p> Signup and view all the answers

    What is the typical 'free' intracellular concentration of calcium ions [Ca2+i] in cells?

    <p>0.1 µM</p> Signup and view all the answers

    Which protein is NOT part of the calcium signaling proteins but rather acts as a calcium binding protein?

    <p>Protein kinase C</p> Signup and view all the answers

    What role do Na+/Ca2+ exchangers like NCX1, NCX2, and NCX3 play in cellular function?

    <p>They actively pump calcium out of cells in exchange for sodium.</p> Signup and view all the answers

    What is the primary characteristic of calcium buffering proteins such as Calnexin and Calsquestrin?

    <p>They bind calcium and help maintain lower concentrations.</p> Signup and view all the answers

    What is the primary function of PMCA in calcium signaling?

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

    Which protein regulates the activity of the SERCA pump?

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

    Which of the following correctly describes NCX function?

    <p>Exchanges 1 Ca2+ for 3 Na+</p> Signup and view all the answers

    What role does the α1 subunit play in voltage-gated calcium channels?

    <p>It contains the ion-selective residues and voltage sensor</p> Signup and view all the answers

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

    <p>4</p> Signup and view all the answers

    Which calcium channel type is primarily associated with pacemaker activity in the heart?

    <p>T-type Ca2+ channels</p> Signup and view all the answers

    What is the main consequence of binding calmodulin to PMCA?

    <p>Increases the movement of Ca2+ out of the cell</p> Signup and view all the answers

    What activates inositol 1,4,5-trisphosphate receptors (IP3R) in calcium signaling?

    <p>Inositol triphosphate (IP3)</p> Signup and view all the answers

    Which calcium transport mechanism is primarily responsible for calcium release from intracellular stores?

    <p>IP3R</p> Signup and view all the answers

    Which of the following statements is true regarding the efficiency of calcium transport by SERCA?

    <p>Transfers 2 Ca2+ for each ATP hydrolyzed</p> Signup and view all the answers

    What is a primary function of Ca2+ -ATPases in cells?

    <p>Maintaining basal Ca2+ levels</p> Signup and view all the answers

    Which of the following statements accurately describes Na+/Ca2+ exchangers?

    <p>They work by exchanging sodium ions for calcium ions across the membrane.</p> Signup and view all the answers

    What role do STIM and Orai receptors play in cellular calcium signaling?

    <p>They regulate membrane calcium flow.</p> Signup and view all the answers

    Which process is primarily driven by the signaling molecule IP3?

    <p>Calcium release from intracellular stores</p> Signup and view all the answers

    In cellular processes, how does calcium function in exocytosis?

    <p>It facilitates the fusion of vesicular membranes with the plasma membrane.</p> Signup and view all the answers

    What is a key characteristic of voltage-gated calcium channels?

    <p>They respond to changes in membrane potential to allow calcium entry.</p> Signup and view all the answers

    Which of the following best describes the functions of calcium binding proteins?

    <p>They modulate the activity of calcium-dependent enzymes and pathways.</p> Signup and view all the answers

    Which cellular function is NOT directly influenced by calcium signaling?

    <p>DNA replication</p> Signup and view all the answers

    How does calcium contribute to long-term potentiation?

    <p>By promoting calcium-dependent protein synthesis</p> Signup and view all the answers

    What effect does calcium have on apoptotic processes?

    <p>It activates pathways leading to cell death.</p> Signup and view all the answers

    What is the role of STIM1 in store-operated calcium entry?

    <p>It senses changes in ER luminal Ca2+ levels.</p> Signup and view all the answers

    Which of the following proteins are essential for facilitating store-operated calcium entry?

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

    How do calcium-binding proteins primarily function in cells?

    <p>By binding and sequestering calcium ions</p> Signup and view all the answers

    What happens to STIM1 upon calcium store-depletion?

    <p>It oligomerizes and translocates to form puncta.</p> Signup and view all the answers

    Which transport mechanism is primarily responsible for calcium egress from the sarcoplasmic reticulum?

    <p>Calcium ATPases</p> Signup and view all the answers

    What effect do gain-of-function mutations in STIM1 have on calcium signaling?

    <p>Enhanced store-operated calcium entry</p> Signup and view all the answers

    Which type of calcium channel is involved in voltage-dependent calcium entry?

    <p>L-type calcium channels</p> Signup and view all the answers

    What primarily limits the sustained increase in cytosolic Ca2+ when relying solely on intracellular stores?

    <p>The finite supply of intracellular Ca2+ stores</p> Signup and view all the answers

    What would be the consequence of a malfunctioning Na+/Ca2+ exchanger (NCX) in a cell?

    <p>Increased levels of intracellular calcium</p> Signup and view all the answers

    Which proteins are primarily responsible for the transport of calcium ions back into the endoplasmic reticulum?

    <p>Ca2+ ATPases</p> Signup and view all the answers

    Study Notes

    Calcium Homeostasis - Part 2

    • Calcium homeostasis occurs both extracellularly and intracellularly.
    • Intracellular calcium is primarily bound by calcium-binding proteins or calcium-buffering proteins within the cytoplasm and cellular organelles like the sarcoplasmic reticulum.

    Calcium Entry & Egress

    • Calcium moves into and out of cells and organelles through a variety of proteins:
    • Ca2+ ATPases:
      • ATP2B (plasma membrane), ATP2A (endoplasmic/sarcoplasmic reticulum) and ATP2C (golgi).
    • Voltage-gated Calcium channels, specifically L-type calcium channels
    • Na+/Ca2+ exchanger (NCX1, NCX2, 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: 25 calcium binding sites located in the endoplasmic reticulum
      • Calsquestrin: 70 calcium binding sites located in the sarcoplasmic reticulum

    Intracellular Calcium Signaling

    • Intracellular calcium plays a role in:
      • Neurotransmitter and hormone release
      • Muscle contraction
      • Cell excitability
      • Calcium-dependent conductance
      • Synaptic plasticity
      • Long-term potentiation
      • Apoptosis
      • Ischemic brain damage
      • Cytoskeletal changes
      • Neurite outgrowth
      • Protein synthesis

    Importance of Calcium

    • Cellular functions reflect unique intrinsic features of calcium, such as its ionic radius and divalent charge.
    • These features allow for discriminating mechanisms for cellular calcium concentration regulation.
    • Specific calcium transporters ensure precise regulation of cellular calcium concentrations.

    Vitamin D Metabolites & NCX

    • NCX belongs to the Ca2+/cation antiporter superfamily.
    • responsible for moving Ca2+ out of the cell.
    • The activity of this exchanger can be modulated by Na+ and Ca2+ binding domains.
    • It's encoded by the SLC8 gene, producing three isoforms: NCX1 (ubiquitous), NCX2 & NCX3 (brain and skeletal muscle)

    Voltage-gated Ca2+ Channels (VGCC/VOC)

    • VGCCs have an alpha (α1) subunit, which contains ion selectivity and the voltage sensor.
    • They have intracellular subunits like beta (β) and extracellular subunits like alpha-2-delta (α2δ), which affect channel trafficking and regulation.
    • VGCCs are encoded by CACNA1 genes.
    • Three subgroups of VGCCs are L-type (skeletal, smooth, cardiac muscle, secretory tissues and nervous system), P/Q-type, N-type and R-type (nervous system) and T-type (neurons and the heart, pacemaker activity).

    Inositol 1,4,5-trisphosphate (IP3)

    • Ca2+ release from intracellular stores (like the endoplasmic reticulum (ER)) is dependent on inositol 1,4,5-trisphosphate receptors (IP3R).
    • IP3R are tetramers of 4 transmembrane spanning helices
    • Phospholipase C (PLC) cleaves PIP2 into IP3 and DAG.

    Store-Operated Calcium Entry (SOCE)

    • SOCE is the process by which Ca2+ enters cells when intracellular Ca2+ stores are depleted.
    • This is facilitated by the proteins STIM1 and Orai.
    • STIM proteins sense changes in the luminal Ca2+ concentration in intracellular stores
    • When these stores deplete, STIM proteins oligomerise and move to the ER/SR-PM. This process attracts Orai proteins.
    • Orai channels then open in the membrane and allow Ca2+ influx.

    SOCE Mutations

    • Mutations in STIM1 have been observed where a gain of function occurs, which increases the SOCE.

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