Calcium ion as a second

messenger
• Calcium ion which is perhaps most common
intracellular messenger in neurons.
• Calcium entry may be initiated by (1) changes in
membrane potential that open calcium channels
or (2) a hormone interacting with membrane
receptors that open calcium channels.
• Example:
• A ligand binds to a calcium channel causing it to open
and let calcium ions into the cell.
• Another example:
• A voltage change across the plasma membrane causes
a voltage sensitive calcium channel to open this
transient rise inside a cytoplasmic Calcium
concentration transmits information within the cell.
• The rise in calcium allows calcium ions to bind to a
large number of calcium binding proteins.
• That serve as molecular targets such as calmodulin
which is abundant in the cytosol of all cells.
• Binding of calcium to calmodulin activates this proteins.
• Calmodulin then activates further signaling pathways by
binding to downstream targets such as protein kinases.
• In order for a rise in intracellular calcium to be sensed by
the cell must carefully maintain resting levels of calcium.
• Ordinarily the calcium concentration in the cytosol is low
about 100 nano molar
• Which is the same as 10^-7.
• The concentration of calcium ions outside neurons is
about a millimolar or 10^-3 molar.
• This deep gradient is maintained by a number of
mechanisms.
• Proteins in the plasma membrane transport calcium
out of the cell.
• One type is a ATPase called a calcium pump.
• The energy from ATP hydrolysis is used to pump
calcium up its concentration gradient while hydrogen
ions are counter transported.
• Another means of maintaining the gradient is by the
action of a sodium calcium exchanger.
• This exchanger uses the energy from a concentration
gradient of sodium ions across the membrane,
exchanging sodium ions for calcium.
• When calcium levels rise within the cell a variety of
calcium binding proteins in addition to calmodulin
bind to the calcium.
• Another Example : calbindin
• Which serves as a calcium ion buffer.
• It reversibly binds calcium and thus blunts the
magnitude and kinetics of calcium signals within
neurons.
• Calcium ions are also pumped into the cells
endoplasmic reticulum.
• The endoplasmic reticulum uses a calcium pumps
similar to that in the plasma membrane.
• As calcium levels fall the signaling systems return to
their resting state through the action of the pumps.
• The ER can serve as storage deport of calcium ions
• That are later released to participate in signaling events.
• Example : channels in the ER allow calcium to be
released from the interior of the endoplasmic reticulum
into the cytosol.
• One such channel is the inositol triphosphate or ip3
receptor
• Which opens when another second messenger ip3
binds to it.
• Another calcium releasing channel is the ryanodine
receptor named after a drug that bind to it.
• Partially open these receptors among the biological
signals that activate ryanodine receptors are
cytoplasmic calium and at least in muscle cells
depolarization of the plasma membrane.
• In these ways calcium ion concentrations are
modulated and used to convey information in the cell.
• Calcium-Calmodulin Second Messenger System:
• Another second messenger system operates in
response to the entry of calcium into the cells.
• On entering a cell, calcium ions bind with the
protein calmodulin.
• This protein has four calcium sites, and when
three or four of these sites have bound with
calcium, the calmodulin changes its shape and
initiates multiple effects inside the cell, including
activation or inhibition of protein kinases.
• Activation of calmodulin-dependent protein kinases
causes, via phosphorylation, activation or inhibition of
proteins involved in the cell’s response to the hormone.
• For example, one specific function of calmodulin is to
activate myosin kinase, which acts directly on the
myosin of smooth muscle to cause smooth muscle
contraction.
• The normal calcium ion concentration in most cells
of the body is 10-8 to 10-7 mol/L, which is not enough
to activate the calmodulin system.
• But when the calcium ion concentration rises to 10-6 to
10-5 mol/L, enough binding occurs to cause all the
intracellular actions of calmodulin.
• This is almost exactly the same amount of calcium ion
change that is required in skeletal muscle to activate
troponin C, which causes skeletal muscle contraction.
• It is interesting that troponin C is similar to calmodulin
in both function and protein structure.
Reference:
• Google, online notes.