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Questions and Answers
Which protein is classified as a calcium binding protein with an EF-hand motif?
Which protein is classified as a calcium binding protein with an EF-hand motif?
What is the primary function of Ca2+-ATPases in muscle contraction?
What is the primary function of Ca2+-ATPases in muscle contraction?
Calcium can enter cells through which of the following mechanisms?
Calcium can enter cells through which of the following mechanisms?
Which of these statements correctly describes the function of the plasma membrane Ca2+ ATPase (PMCA)?
Which of these statements correctly describes the function of the plasma membrane Ca2+ ATPase (PMCA)?
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Which of the following is NOT a type of calcium transporter mentioned?
Which of the following is NOT a type of calcium transporter mentioned?
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Which type of calcium ATPase is responsible for transporting calcium in the sarcoplasmic reticulum?
Which type of calcium ATPase is responsible for transporting calcium in the sarcoplasmic reticulum?
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What is the typical 'free' intracellular concentration of calcium ions [Ca2+i] in cells?
What is the typical 'free' intracellular concentration of calcium ions [Ca2+i] in cells?
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Which protein is NOT part of the calcium signaling proteins but rather acts as a calcium binding protein?
Which protein is NOT part of the calcium signaling proteins but rather acts as a calcium binding protein?
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What role do Na+/Ca2+ exchangers like NCX1, NCX2, and NCX3 play in cellular function?
What role do Na+/Ca2+ exchangers like NCX1, NCX2, and NCX3 play in cellular function?
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What is the primary characteristic of calcium buffering proteins such as Calnexin and Calsquestrin?
What is the primary characteristic of calcium buffering proteins such as Calnexin and Calsquestrin?
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What is the primary function of PMCA in calcium signaling?
What is the primary function of PMCA in calcium signaling?
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Which protein regulates the activity of the SERCA pump?
Which protein regulates the activity of the SERCA pump?
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Which of the following correctly describes NCX function?
Which of the following correctly describes NCX function?
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What role does the α1 subunit play in voltage-gated calcium channels?
What role does the α1 subunit play in voltage-gated calcium channels?
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How many splice variants are produced by the four ATP2B genes encoding PMCA?
How many splice variants are produced by the four ATP2B genes encoding PMCA?
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Which calcium channel type is primarily associated with pacemaker activity in the heart?
Which calcium channel type is primarily associated with pacemaker activity in the heart?
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What is the main consequence of binding calmodulin to PMCA?
What is the main consequence of binding calmodulin to PMCA?
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What activates inositol 1,4,5-trisphosphate receptors (IP3R) in calcium signaling?
What activates inositol 1,4,5-trisphosphate receptors (IP3R) in calcium signaling?
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Which calcium transport mechanism is primarily responsible for calcium release from intracellular stores?
Which calcium transport mechanism is primarily responsible for calcium release from intracellular stores?
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Which of the following statements is true regarding the efficiency of calcium transport by SERCA?
Which of the following statements is true regarding the efficiency of calcium transport by SERCA?
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What is a primary function of Ca2+ -ATPases in cells?
What is a primary function of Ca2+ -ATPases in cells?
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Which of the following statements accurately describes Na+/Ca2+ exchangers?
Which of the following statements accurately describes Na+/Ca2+ exchangers?
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What role do STIM and Orai receptors play in cellular calcium signaling?
What role do STIM and Orai receptors play in cellular calcium signaling?
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Which process is primarily driven by the signaling molecule IP3?
Which process is primarily driven by the signaling molecule IP3?
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In cellular processes, how does calcium function in exocytosis?
In cellular processes, how does calcium function in exocytosis?
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What is a key characteristic of voltage-gated calcium channels?
What is a key characteristic of voltage-gated calcium channels?
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Which of the following best describes the functions of calcium binding proteins?
Which of the following best describes the functions of calcium binding proteins?
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Which cellular function is NOT directly influenced by calcium signaling?
Which cellular function is NOT directly influenced by calcium signaling?
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How does calcium contribute to long-term potentiation?
How does calcium contribute to long-term potentiation?
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What effect does calcium have on apoptotic processes?
What effect does calcium have on apoptotic processes?
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What is the role of STIM1 in store-operated calcium entry?
What is the role of STIM1 in store-operated calcium entry?
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Which of the following proteins are essential for facilitating store-operated calcium entry?
Which of the following proteins are essential for facilitating store-operated calcium entry?
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How do calcium-binding proteins primarily function in cells?
How do calcium-binding proteins primarily function in cells?
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What happens to STIM1 upon calcium store-depletion?
What happens to STIM1 upon calcium store-depletion?
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Which transport mechanism is primarily responsible for calcium egress from the sarcoplasmic reticulum?
Which transport mechanism is primarily responsible for calcium egress from the sarcoplasmic reticulum?
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What effect do gain-of-function mutations in STIM1 have on calcium signaling?
What effect do gain-of-function mutations in STIM1 have on calcium signaling?
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Which type of calcium channel is involved in voltage-dependent calcium entry?
Which type of calcium channel is involved in voltage-dependent calcium entry?
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What primarily limits the sustained increase in cytosolic Ca2+ when relying solely on intracellular stores?
What primarily limits the sustained increase in cytosolic Ca2+ when relying solely on intracellular stores?
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What would be the consequence of a malfunctioning Na+/Ca2+ exchanger (NCX) in a cell?
What would be the consequence of a malfunctioning Na+/Ca2+ exchanger (NCX) in a cell?
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Which proteins are primarily responsible for the transport of calcium ions back into the endoplasmic reticulum?
Which proteins are primarily responsible for the transport of calcium ions back into the endoplasmic reticulum?
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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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