study notes for lecture six: calcium imbalance

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8 Mar 2011
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LECTURE SIX: CALCIUM BALANCE
*ER = endoplasmic reticulum
*SR = sarcoplasmic reticulum
*PLC = phospholipase C
*IP3 = inositol triphosphate
*DAG = diacyl glycerol
*PIP2 = phosphotidylinositol-4,5-bisphosphate
CALCIUM AND NORMAL PHYSIOLOGY
FUNCTION
Considerations
intracellular signalling
- recall: one of the G-SURWHLQFRXSOHGUHFHSWRUV¶VHFRQGPHVVHQJHUV\VWHPWULJJHUHGXSRQepinephrine binding
releases PLC which elevates levels of IP3 and DAG, which results in increase of intracellular [Ca2+]
- consider: alpha-1 adrenergic receptor
- upon activation, a heterotrimeric G protein activates phospholipase C which cleaves PIP2 into both IP3 and DAG
increasing its levels
- IP3 is soluble and diffuses through the cell
- it binds to its receptor on ER and SR opening calcium channels
- results in increase of Ca2+ in cytoplasm and sarcoplasm
- has a positive feedback on SR resulting in increased Ca2+ release
hormone secretion
- process of insulin secretion = rise of intracellular calcium
blood clotting
-
neural excitability
- different statuses of neuronal activity leading to firing of neurons
- there is strict regulation
muscle contraction
-
building and maintaining bone
- strength
calcium spark
Ærecall: glucose stimulates insulin release
Æbefore its release, there is a spike of Ca2+ which serves as a signal
((how is the total calcium in your body maintained))
intake output
diet kidney
small intestine
((how is the total calcium in your body maintained))
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1) Ca2+
Æchannel favours cation movement from lumen side to kidneys
Æbrings calcium into the cell
2) calbindin
Æbinds to calcium to facilitate movement within the cell
3) Na+/Ca2+ exchanger
Æcalcium exits the cell for exchange of 3 sodium ions regulation of excretion
of Ca2+ from blood to
4) Ca2+ ATPase external environment via the kidneys
Æexcretion of calcium via ATPase pump
total body Ca2+ = intracellular + extracellular {ECF/plasma + bone}
*Æmost calcium is bound to proteins
small intestine Æ ECF = extracellular fluid bone = 99% } extracellular matric
0.1%
kidney Æ [Ca2+] 2.5 mM cell = 0.9% } represents Ca2+ used for
Å [free Ca2+] = 0.001mM intracellular signalling
cascades
expect this reading when
calcium is maintained
at homeostatic level
in the blood/ECF
bone is constantly being formed and resorbed
Æcalcium in bone is mainly in crystals = hydroxyapatite {Ca10(PO4)6(OH2)}
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