Download Lecture 23

Got Calcium?
Ca2+
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
– Absorption – Via intestines
– Excretion – Via urine
– Temporary storage – Via bones
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 reabsorption 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
Calcium Signal Transduction in
Parathyroid Gland
600 AA external
domain
• 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
Phosphorylation Gland
sites
200 AA internal
domain
– Regulates calcitonin secretion
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
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)
Hyperparathyroidism
Calcitonin
• Secreted by the thyroid gland
• Effects are much less than those of PTH
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
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