HomeProtein ExpressionCalcium Channels

Calcium Channels

The voltage-gated calcium channels constitute one group of a superfamily of ion channels that also includes sodium and potassium channels and amongst which exists functional, sequence and topological similarities. These channels are a major route of calcium translocation across the plasma membranes of excitable cells and serve to support multiple functions, including muscle contraction, hormone and neurotransmitter release, cell motility, cell growth and regulation, cell damage and death and finally cell survival.

There are at least six classes of voltage-gated calcium channels that are differentially distributed according to cell type and location and that may be distinguished by electrophysiological, pharmacological and structural characteristics. Several therapeutically effective drugs, including verapamil, nifedipine, diltiazem and second-generation 1,4-dihydropyridine analogs of nifedipine, interact at the L-type channel and are widely used in the treatment of hypertension and certain cardiovascular disorders.

The voltage-gated calcium channel is a hetero-multimer being composed of α1, α2-δ, and β subunits and, for skeletal muscle, the γ subunit. The α1 subunit is the major functional unit of the channel, expressing the permeation and gating functions and, at least in the case of the L-type channels, the drug binding sites. However, the other subunits, notably the β subunit, have significant impact on the expression and electrophysiological characteristics of the channel. Additionally, the α2-δ subunit may also be involved in drug binding, notably for gabapentin. There are 10 α1 subunits (Cav1.1-1.4, formerly α1S, α1C, α1D and α1F; Cav2.1-2.3, formerly α1A, α1B and α1E; Cav3.1-3.3, formerly α1G, α1H and α1I) and four β subunits (β1-4) known with splice variants of each. The α1 subunits are large membrane proteins composed of four homologous domains, I-IV, with each domain composed of six transmembrane helices and a pore region between helices five and six. The S4 segments contain specific arrays of positive charges that are assigned to a voltage-sensing function. The Cav1.2-1.4 genes code for the α-subunits of the L-type channels of the cardiac and neuronal/endocrine types and Cav1.1 codes for the L-type channels of skeletal muscle. The Cav2.1–2.3 genes code for the N-, P/Q and R-type channels. The functional properties and expression of the α subunits are substantially modified by the presence of β subunits. It is likely that channel subclasses are produced by α-β subunit interactions as well as by splice variations. The Cav3.1-3.3 subunits code for the T-type channel, the most recently cloned channel.

Although electrophysiological differences do exist between the channel classes, the most obvious distinctions are between the T- and the other types. T-type channels need only small depolarizations to be activated and are known as low-voltage-activated (LVA) and they deactivate slowly. In contrast, the other classes all require larger depolarizations to be activated and are known as high-voltage-activated (HVA) channels. Although there are electrophysiological distinctions among the HVA channels, they are not sufficiently precise as to permit unambiguous differentiation solely by these criteria. Additionally, it is likely that subclasses of each of these channel types exist with different biophysical properties. At present, pharmacological differentiation is the best route for differentiating the HVA channels.

The L-type channels are well characterized by small synthetic ligands – verapamil, nifedipine and diltiazem – and the T-type channel is described as preferentially blocked by mibefradil, a structurally distinct entity that was in clinical use albeit it was recently withdrawn. All of these entities interact with their channel targets in a voltage-dependent manner, with the greater affinity being exhibited for the open and inactivated states of the channel. The N-, P- and Q-type channels are sensitive to peptide toxins from molluscs and spiders, including the conotoxins and the agatoxins. The conotoxins GVIA and MVIIA interact with the N-type channels with nanomolar potencies; MVIIC interacts with both N and P/Q types and agatoxin IVA interacts selectively with the P/Q types of channel. No small organic ligands are clinically available for other than the L-type channel, although there are a number of experimental compounds for the T- and N-type channels.

The Table below contains accepted modulators and additional information. For a list of additional products, see the "Similar Products" section below.


a) ~l00 mM Ba2+ as charge carrier.

b) Sensitive refers to concentrations < 1 µM; insensitive refers to concentrations > 1 µM.

c) Mibefradil is not very selective for T-type currents; ethosuximide (E7138) and congeners maybe more selective, although of lower affinity.

Similar Products


Arikkath J, Campbell KP. 2003. Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Current Opinion in Neurobiology. 13(3):298-307.
Ertel EA, Campbell KP, Harpold MM, Hofmann F, Mori Y, Perez-Reyes E, Schwartz A, Snutch TP, Tanabe T, Birnbaumer L, et al. 2000. Nomenclature of Voltage-Gated Calcium Channels. Neuron. 25(3):533-535.
Jagannathan S, Publicover S, Barratt C. 2002. Voltage-operated calcium channels in male germ cells.203-215.
Kochegarov AA. 2003. Pharmacological modulators of voltage-gated calcium channels and their therapeutical application. Cell Calcium. 33(3):145-162.
Lorenzon NM, Beam KG. 2000. Calcium channelopathies. Kidney International. 57(3):794-802.
McDonough SI. 2004. Calcium Channel Pharmacology.
Miljanich GP, Ramachandran J. 1995. Antagonists of Neuronal Calcium Channels: Structure, Function, and Therapeutic Implications. Annu. Rev. Pharmacol. Toxicol.. 35(1):707-734.
Monteith GR, Davis FM, Roberts-Thomson SJ. 2012. Calcium Channels and Pumps in Cancer: Changes and Consequences. J. Biol. Chem.. 287(38):31666-31673.
Nimmrich V, Gross G. 2012. P/Q-type calcium channel modulators. 167(4):741-759.
Ophoff R, Terwindt GM, Ferrari M, Frants R. 1998 Genetics and pathology of voltage-gated Ca2+ channels Histol. Pathol . Genetics and pathology of voltage-gated Ca2+ channels Histol.. Pathol. 13 827-836.
Perez-Reyes E. 2003. Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels. Physiological Reviews. 83(1):117-161.
Ross WN. 2012. Understanding calcium waves and sparks in central neurons. Nat Rev Neurosci. 13(3):157-168.
Scott R, Martin D, McClelland D. 2003. Cellular Actions of Gabapentin and Related Compounds on Cultured Sensory Neurones. CN. 1(3):219-235.
Shorofsky SR, Balke C. 2001. Calcium currents and arrhythmias: insights from molecular biology. The American Journal of Medicine. 110(2):127-140.
Suzuki Y, Inoue T, Ra C. 2010. L-type Ca2+ channels: A new player in the regulation of Ca2+ signaling, cell activation and cell survival in immune cells. Molecular Immunology. 47(4):640-648.
Triggle DJ, Langs DA, Janis RA. 1989. Ca2+ channel ligands: Structure-function relationships of the 1,4-dihydropyridines. Med. Res. Rev.. 9(2):123-180.
Venetucci L, Denegri M, Napolitano C, Priori SG. 2012. Inherited calcium channelopathies in the pathophysiology of arrhythmias. Nat Rev Cardiol. 9(10):561-575.
Yagami T, Kohma H, Yamamoto Y. 2012. L-Type Voltage-Dependent Calcium Channels As Therapeutic Targets for Neurodegenerative Diseases. CMC. 19(28):4816-4827.
Sign In To Continue

To continue reading please sign in or create an account.

Don't Have An Account?