Session 4: Calcium ion channels, pumps and receptors and intracellular calcium Flashcards
Name physiological processes where calcium plays a key role and identify the form of calcium actively involved in these processes.
Physiological processes:
- cell proliferation, neural signaling, transmission of nerve impulses, learning (short term memory), muscle contraction, blood clotting, bone formation, fertilisation and activation B lymphocytes.
Form of calcium: Ca++
Compare the average normal interstitial and intracellular calcium ion concentrations.
Interstitial: 2.4 mEq/L
Intracellular: 0.0001 mEq/L
Identify two important storage sites of calcium.
- Smooth surfaced ER
- Mitochondria
Identify intracellular calcium-binding proteins and state the specific functions of two of the most important ones involved in muscle contraction.
Calmodulin: accepts intracellular Ca++ to form a calcium-calmodulin
Troponin: accepts intracellular Ca++ and then undergoes a conformational change that alters the position of tropomyosin
Identify the maximum number of calcium ions that can bind to troponin C and calmodulin respectively.
Four
Identify different types of ion channels, pumps and receptors and identify at least one prominent location for a calcium ion channel, a calcium ion pump and a calcium ion receptor, respectively.
CALCIUM ION RECEPTORS:
* Plasmalemma Ca++ receptors in the parathyroid
glands
* Plasmalemma Ca++ receptors in bone
CALCIUM ION CHANNELS:
* Plasmalemma voltage-gated Ca++ in the SR
membrane
* Plasmalemma ligand-gated Ca++ channels, e.g. IP3
receptor associated ligand gated Ca++ channel
CALCIUM ION PUMPS:
- Ca++/H+ ATPase pump in the plasma/-sarcolemma
- Mg++/Ca++ ATPase in the SR membrane
State the location and function of calcium ion pumps systems involved in primary and secondary active transport.
PRIMARY ACTIVE TRANSPORT:
- Function: one calcium ion is pumped out of the cell for
two hydrogen ions (Ca++/H+ pump)
- Location: in the CM or one or more intracellular
vesicular organelles, such as SR of muscle cells and
mitochondria in all cells
SECONDARY ACTIVE TRANSPORT:
- Function: one calcium ion is transported out the cells
by an antiport driven by the Na+ gradient &
exchanges 3 Na ions for each (Na+/Ca++ pump)
- Location: in al/almost all membranes
Identify two anatomical locations of the dihydropyridine receptors and indicate one important difference between these two types of DHP receptors.
Skeletal and cardiac muscle at junctions of T-tubules and sarcoplasmic reticulum.
- Difference = one is functionally coupled to a protein
Briefly describe the functional role of the ryanodine “receptors”/”receptor channels” in cardiac and skeletal muscle.
- In the skeletal muscle, the dihydropyridine (DHP)
receptor in the T tubule membrane “pulls” a foot
process away from the ryanodine receptor Ca++
release channel in the SR membrane. - The release of Ca++ from the SR initiates muscle contraction.
Relate the four depolarisation and plateau phases of the cardiac muscle action potential to extracellular and intracellular calcium ion concentrations, calcium ion movement.
Phase 1 (initial repolarisation), fast sodium channels close: The sodium channels close, the cell begins to repolarise, and potassium ions leave the cell through the open potassium channels.
Phase 2 (plateau), calcium channels open and fast potassium channels close:
*A brief initial repolarisation occurs and the action
potential then plateaus as a result of increased
calcium ion permeability and decreased potassium
permeability.
*The voltage-gated calcium ion channels open slowly during phases 1 and 0, and calcium enters the cell. Potassium channels then close , and the combination of decreased potassium ion efflux and increased calcium ion influx causes the action potential plateau.
Phase 3 (rapid repolarisation), calcium channels close and slow potassium channels open: The closure of calcium ion channels and increased potassium ion permeability, permitting potassium ions to rapidly exit the cell, ends the plateau and returns the cell membrane potential to its resting level.
Phase 4 (resting membrane potential) averages about -90 mV
Provide two definitions for the term “muscle contracture”.
Definition 1: Sustained contraction since ATP is necessary for muscle contraction and relaxation. If transport back into the SR is inhibited (e.g. due to hypoxia, with less ATP available), relaxation cannot occur even if action potentials have ceased.
Definition 2: Permanent muscle shortening.
Briefly explain the mechanism of tetanization in skeletal muscle and identify two pathological causes thereof.
- A single action potential results in release of a
standard amount of Ca++ from SR which results in a
single twitch. - If muscle is stimulated repeatedly, more Ca++ is
released from SR, with a greater rise in intracellular
Ca++, and greater cross-bridge formation. - As a result, more tension is generated by muscle
(tetanization. Under normal circumstances,
tetanization does not occur in the heart
Two pathological causes: hypocalcemia and the tetanus toxin produced by the anaerobic bacterium Clostridium tetani (which can cause death due to malfunction of respiratory muscles)
Briefly describe the clinical importance of Ca++ receptors.
Certain calcium ion receptors prevent apoptosis.
Calcium ion receptors can respond to different endogenous or exogenous agonists or modulators of receptor activity.
Calcium ion receptors are important targets for development of therapeutic agents, which are required where calcium ion receptors are over-or-under active.
