Voltage-dependent calcium channels (
VDCC) are a group of
voltage-gated ion channels found in the
membrane of excitable cells (
e.g.,
muscle,
glial cells,
neurons, etc.) with a
permeability to the
calcium ion Ca
2+. These channels are slightly permeable to
sodium ions, so they are also called Ca
2+-Na
+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At
physiologic or resting
membrane potential, VDCCs are normally closed. They are activated (
i.e., opened) at
depolarized membrane potentials and this is the source of the "voltage-dependent"
epithet. The concentration of
calcium (Ca
2+ ions) is normally several thousand times higher outside of the cell than inside. Activation of particular VDCCs allows Ca
2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive
potassium channels,
muscular contraction, excitation of neurons, up-regulation of
gene expression, or release of
hormones or
neurotransmitters. VDCCs have been immunolocalized in the
zona glomerulosa of normal and hyperplastic human
adrenal, as well as in
aldosterone-producing
adenomas (APA), and in the latter T-type VDCCs correlated with plasma aldosterone levels of patients. Excessive activation of VDCCs is a major component of
excitotoxicity, as severely elevated levels of intracellular calcium activates enzymes which, at high enough levels, can degrade essential cellular structures.