T-type calcium channel

T-type calcium channels are low voltage activated calcium channels that become inactivated during cell membrane hyperpolarization but then open to depolarization. The entry of calcium into various cells has many different physiological responses associated with it. Within cardiac muscle cell and smooth muscle cells voltage-gated calcium channel activation initiates contraction directly by allowing the cytosolic concentration to increase. Not only are T-type calcium channels known to be present within cardiac and smooth muscle, but they also are present in many neuronal cells within the central nervous system. Different experimental studies within the 1970s allowed for the distinction of T-type calcium channels (transient opening calcium channels) from the already well-known L-type calcium channels (Long-Lasting calcium channels). The new T-type channels were much different from the L-type calcium channels due to their ability to be activated by more negative membrane potentials, had small single channel conductance, and also were unresponsive to calcium antagonist drugs that were present.[1] These distinct calcium channels are generally located within the brain, peripheral nervous system, heart, smooth muscle, bone, and endocrine system.[2]

The distinct structures of T-type calcium channels are what allow them to conduct in these manners, consisting of a primary α1 subunit. The α1 subunit of T-type channels is the primary subunit that forms the pore of the channel, and allows for entry of calcium.

T-type calcium channels function to control the pace-making activity of the SA Node within the heart and relay rapid action potentials within the thalamus. These channels allow for continuous rhythmic bursts that control the SA Node of the heart.[3]

Pharmacological evidence of T-type calcium channels suggest that they play a role in several forms of cancer,[4] absence epilepsy,[5] pain,[6] and Parkinson's disease.[7] Further research is continuously occurring to better understand these distinct channels, as well as to create drugs to selectively target these channels.

Calcium channel, voltage-dependent, T-type, alpha 1G subunit
Identifiers
SymbolCACNA1G
IUPHAR535
HGNC1394
OMIM604065
RefSeqNM_018896
UniProtO43497
Other data
LocusChr. 17 q22
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StructuresSwiss-model
DomainsInterPro
Calcium channel, voltage-dependent, T-type, alpha 1H subunit
Identifiers
SymbolCACNA1H
IUPHAR536
NCBI gene8912
HGNC1395
OMIM607904
RefSeqNM_001005407
UniProtO95180
Other data
LocusChr. 16 p13.3
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StructuresSwiss-model
DomainsInterPro
Calcium channel, voltage-dependent, T-type, alpha 1I subunit
Identifiers
SymbolCACNA1I
IUPHAR537
NCBI gene8911
HGNC1396
OMIM608230
RefSeqNM_001003406
UniProtQ9P0X4
Other data
LocusChr. 22 q13.1
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StructuresSwiss-model
DomainsInterPro
  1. ^ Catterall WA (August 2011). "Voltage-gated calcium channels". Cold Spring Harbor Perspectives in Biology. 3 (8): a003947. doi:10.1101/cshperspect.a003947. PMC 3140680. PMID 21746798.
  2. ^ Iftinca MC (May 2011). "Neuronal T-type calcium channels: what's new? Iftinca: T-type channel regulation". Journal of Medicine and Life. 4 (2): 126–138. PMC 3124264. PMID 21776294.
  3. ^ Perez-Reyes E (January 2003). "Molecular physiology of low-voltage-activated t-type calcium channels". Physiological Reviews. 83 (1): 117–161. doi:10.1152/physrev.00018.2002. PMID 12506128.
  4. ^ Dziegielewska B, Gray LS, Dziegielewski J (April 2014). "T-type calcium channels blockers as new tools in cancer therapies". Pflügers Archiv. 466 (4): 801–810. doi:10.1007/s00424-014-1444-z. PMID 24449277. S2CID 18238236.
  5. ^ Nelson MT, Todorovic SM, Perez-Reyes E (2006). "The role of T-type calcium channels in epilepsy and pain". Current Pharmaceutical Design. 12 (18): 2189–2197. doi:10.2174/138161206777585184. PMID 16787249.
  6. ^ Todorovic SM, Jevtovic-Todorovic V (April 2014). "Targeting of CaV3.2 T-type calcium channels in peripheral sensory neurons for the treatment of painful diabetic neuropathy". Pflügers Archiv. 466 (4): 701–706. doi:10.1007/s00424-014-1452-z. PMID 24482063. S2CID 15152953.
  7. ^ Bermejo PE, Anciones B (September 2009). "A review of the use of zonisamide in Parkinson's disease". Therapeutic Advances in Neurological Disorders. 2 (5): 313–317. doi:10.1177/1756285609338501. PMC 3002602. PMID 21180621.