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Got Calcium?

Got Calcium?. Ca 2+. Plasma Calcium Regulation. Plasma calcium totals 2.4 mM (9.4 mg/dl) Free calcium is 1.2 mM. Plasma Calcium Regulation. Free calcium is tightly regulated ( 5%) Too low = neuronal hyper-excitability Too high = neuronal depression Control points for calcium

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Got Calcium?

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  1. Got Calcium? Ca2+

  2. Plasma Calcium Regulation • Plasma calcium totals 2.4 mM (9.4 mg/dl) • Free calcium is 1.2 mM

  3. Plasma Calcium Regulation • 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

  4. Active Control of Calcium • Vitamin D3 • Diet and sun • Parathyroid hormone • Parathyroid gland • Calcitonin • Thyroid gland • Skeletal loading • Osteoblasts and osteoclasts

  5. 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)

  6. 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

  7. 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

  8. Parathyroid Hormone

  9. Calcium Signal Transduction in Parathyroid Gland • 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 600 AA external domain Phosphorylation sites 200 AA internal domain

  10. Effects of PTH • 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

  11. Other 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)

  12. Hyperparathyroidism

  13. Calcitonin • Secreted by the thyroid gland • Effects are much less than those of PTH

  14. Effects of Calcitonin • 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

  15. 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

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