Biology Reference
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membrane underneath to small monovalent cations, thereby allowing the entire cell
to be voltage-clampedwithout disrupting its contents, the integrated activity of all the
calcium channels in the surface membrane can be measured.
I. Introduction
Calcium ions trigger many fundamental cellular processes by binding to pro-
teins, usually with dissociation constants around 1 m M calcium. However, unlike
other second messengers such as cyclic nucleotides, calcium is neither created nor
destroyed by biological processes. Therefore, regulating calcium-dependent pro-
cesses requires moving calcium ions into and out of cellular compartments. Trans-
port proteins that hydrolyze ATP move calcium ions from lower to higher
concentrations. They maintain resting cytoplasmic calcium at 100-200 nM by
pumping calcium out of the cytosol into the endoplasmic reticulum, the mitochon-
dria, or out across the plasma membrane. By contrast, ion channel proteins, when
the channels are open, allow calcium ions to di
use rapidly down their electro-
chemical gradient back into the cytosol. Many channels are permeable to calcium
because they pass all cations, including calcium, up to a certain size, but most of
the current is carried by more prevalent ions such as sodium or potassium. In
contrast, some ''calcium-selective'' channels pass calcium almost exclusively, even
in the presence of other cations.
There are currently three classes of calcium-selective channel proteins ( Table I ):
three families of voltage-gated calcium channels in the plasma membrane (CaV1-3);
two families of calcium-selective channels in the endoplasmic reticulum membrane;
V
Table I
Calcium-selective channels
Voltage-activated calcium channels in the surface membrane
L type
CaV1.1
CACNA1S
Skeletal muscle
CaV1.2
CACNA1C
Cardiovascular muscle
CaV1.3
CACNA1D
Endocrine cells, neurons
CaV1.4
CACNA1F
Retina
P/Q type
CaV2.1
CACNA1A
Nervous system
N type
CaV2.2
CACNA1B
Nervous system
R type
CaV2.3
CACNA1E
Nervous system
T type
CaV3.1
CACNA1G
Brain, heart
CaV3.2
CACNA1H
Brain, endocrine cells, heart
CaV3.3
CACNA1I
Brain
Calcium release-activated channel (CRAC) in the surface membrane
STIM-gated ORAI1-3?
Ligand-gated calcium channel in the endoplasmic reticulum
IP 3 -gated
ITPR1-3
Ryanodine-gated
RYR1-3
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