Calcium Homeostasis at the Cellular Level

Calcium

Ca⁺⁺ binds tightly to proteins because of divalence

extracellular 2.5 mM total; 1.3 mM unbound

intracellular 100 nM unbound; 10, 000x difference

Ca⁺⁺ ATPases also pump Ca⁺⁺ into ER (1 mM)

mito can take up Ca⁺⁺ using H⁺ gradient if necessary

The Importance of Calcium

(1) muscle contraction

(2) hormone/neurotransmitter secretion

(3) cell division

(4) directed migration of cells

(5) visual processing

(6) regulation of carb metabolism

Calmodulin

binds Ca⁺⁺ with high affinity (4 sites)

mM levels of Ca⁺⁺ will fill sites, change conformation so can bind to other regulatory proteins

Ca⁺⁺ Channels – major route of Ca⁺⁺ release into cytoplasm

(1) Voltage gated – L-type (long lasting), T-type (transient), N-type (neuronal)

(2) Ligand Gated

cardiac muscle – Ca⁺⁺ activated (i.e. from voltage gated channels)
skeletal muscle - direct protein-protein interactions with DHP sensitive L-type receptors
ryanodine

Na⁺/Ca⁺⁺ Exchange Transporter

used after repeated or prolonged stimulation of Ca⁺⁺ channels

digitalis affects Na⁺/Ca⁺⁺ exchanger indirectly through Na⁺,K⁺ ATPase

Ca⁺⁺ ATPase Transporters

(1) plasma membrane – calmodulin (+) so Ca (+)

(2) ER/SR form – unregulated

(3) Cardiac SR – high affinity