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Got Calcium? Ca2+
Plasma Calcium Regulation
• Plasma calcium totals 2.4 mM (9.4 mg/dl)– Free calcium is 1.2 mM
• Free calcium is tightly regulated (5%)– Too low = neuronal hyper-excitability– Too high = neuronal depression
• Control points for calcium– Absorption – Via intestines– Excretion – Via urine– Temporary storage – Via bones
Plasma Calcium Regulation
Active Control of Calcium
• Vitamin D3– Diet and sun
• Parathyroid hormone– Parathyroid gland
• Calcitonin– Thyroid gland
• Skeletal loading– Osteoblasts and osteoclasts
Vitamin D3 and Calcium Control
• Vitamin D3 (Cholecalciferol)– Converted to precursor in liver
• Initially stored• Converted to 25-Hydroxycholecalciferol• Feedback control limits concentration
– Converted to active form in kidney • 1,25-Dihydroxycholecalciferol• Under the feedback control of parathyroid
hormone (PTH)
Effects of Active Form of Vit D3• Promotes intestinal absorption of calcium• Causes synthesis of calcium-binding protein
and related facilitated transport• Takes a couple of days to fully develop
response• Has slight effect to increase calcium re-
absorption in kidneys• Works with PTH to cause calcium absorption
from bone
Parathyroid Hormone• Secreted by parathyroid glands
– Rapid response to reduced calcium (minutes)
• Polypeptide – 84 amino acid residues
– 9,500 daltons M.W.
• Peptide fragments can be active for periods measured in hours
• Operates in tissues via cAMP second messenger
Parathyroid Hormone
• G-Protein Coupled Receptor
• Activates Phospholipase C– Leads to increased Diacylglycerol (DG)
and Inositol trisphosphate (IP3) as secondary messengers
– Inhibits adenylate cyclase to reduce cAMP
• Present in C cells of Thyroid Gland– Regulates calcitonin secretion
Calcium Signal Transduction in Parathyroid Gland
600 AA externaldomain
200 AA internaldomain
Phosphorylationsites
• Increases calcium absorption from bone– Existing osteocytes stimulated (minutes to
hours) to transport calcium – calcium pumps– Existing osteoclasts activated and new
osteoclasts formed (days to weeks) to digest bone and release calcium
• Stimulated indirectly by osteoblasts
Effects of PTH
• Decreases excretion of calcium by kidneys– Important to prevent bone deterioration
• Increases calcium absorption– Effect manifested via Vitamin D3
• Produces most active form of D3 in the kidney (1,25-dihydroxy-cholecalciferol)
Other Effects of PTH
Hyperparathyroidism
Calcitonin• Secreted by the thyroid gland
• Effects are much less than those of PTH
• Attenuates absorptive ability of osteoclasts
• Inhibits formation of new osteoclasts– Osteoclast decrease causes osteoblast
decrease– Effect to decrease calcium is transitory– Causes reduced bone turnover
• Has weak effect in kidney and intestines
Effects of Calcitonin
Non-Hormonal Control of Plasma Calcium
• Changes in calcium intake can be rapidly accommodated – Buffer capacity of amorphous calcium in
bone– Calcium is sequestered in intracellular
spaces– Can help restore plasma calcium in tens of
minutes