Transcript MARKSPHARM030603A.ppt

Why Calcium?
Double positive charge provides increased affinity f or negatively c harged proteins
but lower affinity than l arger divalent cations suc h as Cu, Zn, or Mn. Th e
coordination c hemistry of Ca is higher and more flexible tha n for Mg.
The fact that Ca complexes wi th i norganic compound s and to proteins s uggests
that the maintenance of low [Ca] intracellularly w ould require less energy than for
other cations. The maintenance of a large transmembrane gradient is critical for
a second messanger ion.
This l arge transmembrane gradient p rovides the signal-to-noise ratio required for
efficient signal transduction.
Resting intracellular [Ca] is ~100 nM versus mM extracellular [Ca] or a
concentra tion gradient of ~10,000.
NCE
mM [Ca]
NMDA, AMPA rec
nAChR
CNG
VR/temp rec
Stretch receptor
TRP
VDAC
mM [Ca]
SOC
IP3R
SERCA
ROC
VGCC
PMCA
mM [Ca]
RyR
SERCA
100 nM [Ca]
Sarcoplasmic Reticulum (SR) / T
Tubule System
Twitch
Summation
Tetanus
Role of Ca++ in contraction