DefinitionThis section has been translated automatically.
For Ca2+-ions selective, transmembrane ion channel, which reacts to the membrane potential of the cell (see also under voltage-dependent ion channel)
Voltage-dependent calcium channels play a central role in the regulation of intracellular Ca2+ concentration and thus contribute to signal processing in numerous cells. The opening of the calcium channels is primarily determined by the membrane potential of the cell, but is also influenced by hormones, protein kinases, phosphatases, toxins and drugs.
If the cell is depolarized, the voltage-dependent Ca2+ channels open. Ca2+ ions flow through the opened cell membrane pores into the cell interior. Voltage-dependent Ca2+ channels are expressed in electrically excitable cells (muscle cells, neurons, endocrine cells). They are involved in muscle contractions, gene expression, neurotransmitter and hormone release, enzyme activities and pain generation (especially N-type calcium channels).
ClassificationThis section has been translated automatically.
In principle, the Ca+ channels can be divided into:
- HVA channels (HVA for high voltage activated): calcium channels activated by high voltage
- LVA channels (LVA for low voltage activated): Calcium channels with a significantly lower action potential (threshold potential more negative than -50mV) expressed in skeletal and cardiac muscle cells and in neurons of the CNS. They generate a long-lasting current because their inactivation is slow.
An earlier classification distinguished 5 channel types (T, L, N, P/Q and R channels). T,L and N were named "transient, long lasting and neither T-nor T". The other designations follow the alphabet.
- T-type channels (T=transient) are expressed in sinus node, thalamus, peripheral nervous system, endocrine cells and smooth muscle cells. T-type channels belong to the LVA channels)
- L-type channels (L=long lasting); this type of channel provides a long lasting inward current that is hardly inactive.
- N-type channels in CNS (N=neither T nor L) especially nociceptive nerve endings), heart and endocrine cells detectable
- P/Q-type channels detectable in the CNS, especially the Purkinje cells of the cerebellum, as well as in heart and endocrine cells
- R-type channels detectable in CNS, heart and endocrine cells
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General informationThis section has been translated automatically.
Voltage-gated calcium channels consist of four pore-forming α1 protein complexes and up to 5 subunits, the β, α2δ, and γ auxiliary subunits (Hofmann et al., 1999). The 4 α1 subunits form the actual Ca2+-active channel. The pore structure is where the different channel types differ.
The most important functional unit is the pore-forming α1 subunit. The remaining subunits have modulatory functions and are referred to as β, α2δ, and γ auxiliary subunits. Based on electrophysiological measurements, L-, N-, P-, Q-, R-, and T-type channels can be distinguished. This diversity is also reflected by the number of calcium channel genes. To elucidate the numerous physiological functions in which calcium channels are involved.
Analogous to the different functional states in Na+ channels, Ca+ channels are also distinguished between 3 states of activity:
- resting state
- activated state
- inactivated state.
There are 10 known genes encoding α1 subunits, 4 for β, 4 for α2δ and 8 for γ.
Clinical pictureThis section has been translated automatically.
LVA channels are blocked by some ethosuximide-type anticonvulsants.
Other antiepileptic drugs block HVA channels(gabapentin and pregabalin. They prevent the influx of Ca2+ into CNS neurons and thus exocytotic transmitter release.
The N-type calcium channel can be blocked by conotoxins (neurotoxic marine toxins of cone snails). Conotoxins are precursors for a group of analgesically active pharmaceuticals (e.g. the peptide ziconotide).
Mutations: Congenital disorders of calcium channels appear to be responsible for:
- hypokalemic periodic paralysis
- malignant hyperthermia
- central core myopathy
- congenital deafness (KCNQ4) and
- certain forms of night blindness.
A dysfunction of KCNN3, a calcium-dependent potassium channel, is also suspected in schizophrenia.
Note(s)This section has been translated automatically.
The long-lasting calcium channels are expressed in the human organism in smooth muscle (e.g. in the vascular walls), in the cardiovascular system and also in neurons.
In smooth muscle and in cardiac muscle, the "long-lasting calcium channels" are essential. They allow a slow calcium influx into the cell during cell membrane depolarization and are essential for electromechanical coupling. Selective calcium antagonists, also known as L-channel blockers, are important therapeutic agents in cardiovascular disease.
In striated muscle cells, L-type calcium channels are located in the cell membrane of the transverse system (T-tubules). In cardiac muscle cells, they are located at the surface membrane. Therefore, in the heart they are binding sites for drugs from the group of dihydropyridines, which block these channels and exert an antihypertensive effect.
LiteratureThis section has been translated automatically.
- Boycott KM et al (2001) A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants. Hum Genet. 108:91–97
- Ertel EA et al (2000) Nomenclature of voltage-dependent calcium channels. Neuron 25: 533-535
- Hofmann F et al (1999) Voltage-dependent calcium channels: From structure to function. Rev. Physiol. Biochem. Pharmacol. 13:, 33-87
- Jurkatt-Rott K et al (1994) A calcium channel mutation causing hypokalemic periodic paralysis. Hum. Mol. Gen. 3: 1415-1419
- Meindl, A. (1998): An L-type calcium channel gene mutated in incomplete X-linked congenital stationary night blindness. Nature Genet. 19: 260–263
- Ophoff RA et al (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene Cacnl1a4. Cell 87: 543-552
- Pereverzev A et al (2002) Disturbances in glucose tolerance, insulin, release, and stress-induced hyperglycemia upon disruption of the Cav 2.3 (α1E) subunit of voltagegated Ca2+ channels. mol. endocrinol. 16: 884-895
- Platzer J et al (2000) Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102, 89-97
- Saegusa H et al (2001) Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J. 20: 2349-2356