194 GROUP I AND II METALS IN BIOLOGICAL SYSTEMS
attraction, because ions must pass through the channel and not be bound to
it. Ions may not necessarily be too small to enter the channel but rather may
carry a large shell of hydration that is energetically disadvantageous to remove.
Larger ions may not enter a given channel based directly on their too - big - to - fi t
size. If neither the hydration shell nor size considerations prevent ions from
entering a channel, then other factors such as gates come into play. Gates, also
known as selectivity fi lters, are kinetic devices allowing or preventing the free
fl ow of ions. Gates may also be charge movement facilitators based on elec-
trostatic cell potentials. A theme common to the hundreds of known ion chan-
nels — gates, selectivity fi lters — is a central cavity or pore(s) through which,
during gating, ions fl ow depending on their charge, size, and concentration.
Protons have their own selective channels that maintain an optimum pH for
various cellular systems. Proton channels will not be discussed further here.
Interested readers should read recent publications inScience magazine for
further details.^10
5.2.3 Calcium Homeostasis,
Phosphorus homeostasis (see Section 5.2.1 ) is intimately involved with that of
calcium. The most important reservoir of calcium and phosphorus within the
mammalian body is in bone — 85% of the body ’ s calcium and 85 – 90% of phos-
phorus is found there. Ninety - nine percent of bone calcium remains in the
mineral phase as Ca 3 (PO 4 ) 2 , and so on, but the other 1% can rapidly exchange
with extracellular calcium.
Free calcium ions act as secondary messengers and function within the cell
in response to an extracellular agent. Other secondary messengers include
cyclic nucleotides such as cAMP (cyclic adenosine monophosphate) and cGMP
(cyclic guanosine monophosphate). Primary messengers include hormones —
insulin, for example — and metabolites such as glucose. Primary messengers
operate in the extracellular environment and effect communication between
cells or respond to changes in the extracellular environment. Chapter 7 of
reference 1 contains a more complete discussion.
In extracellular fl uids, about half of Ca 2+ ions are bound to proteins. Free
calcium ions have a concentration of approximately 2 mM in blood as seen in
Tables 5.1 and 5.2 , with the concentration of phosphate ions being similar.
Intracellularly, Ca 2+ is held within mitochondria and in the endoplasmic reticu-
lum. The intracellular concentration of calcium ions in blood is about 10 − 4 m M
(10^2 nM) as seen in Tables 5.1 and 5.2. Intracellular calcium ion concentration
may fl uctuate between 10^2 and 10^3 nM as Ca 2+ is released from cellular stores
or infl uxes from the extracellular fl uid. These fl uctuations are integral to cal-
cium ’ s role in intracellular signaling, enzyme activation, and muscle contrac-
tion. Some proteins and enzymes involved in binding and releasing calcium
ions are, for example: (1) Troponin C (binding of Ca 2+ results in muscle con-
traction), (2) calmodulin (binding of Ca 2+ activates enzymes such as protein
kinases), and (3) Ca 2+ - ATPases (cross - membrane calcium pumps binding and