Calcium channels subunits

Voltage-dependent Ca2 Channels. Figure 1 Structure, identity and blockers of calcium channel subunits. 

Hans M, Luvisetto S, Williams ME, Spagnolo M, Urrutia A, Tottene A, Brust PF, Johnson EC, Harpold MM, Stauderman KA, Pietrobon D (1999) Functional consequences of mutations in the human alphalA calcium channel subunit linked to familial hemiplegic migraine. J Neurosci 19 1610-1619. 

Table 1 Comparison of the physiological, pharmacological, and electrophysiological characteristics of voltage-gated calcium channel subunit subtypes... 

The calcium channel p subunit is the only calcium channel subunit for which there is crystal structure information. The core of this subunit is homologous to membrane-associated guanylate kinases (MAGUKs), with conserved, interacting SH3 and guanylate kinase (GK) domains (Takahashi et al. 2004). Residues in the... 

It has been known for a long time that the skeletal muscle L-type calcium channel complex also contains a y subunit - a four transmembrane helix with cytoplasmic bland C-termini (Arikkath and Campbell 2003). Seven additional potential candidates for neuronal calcium channel y subunits have been identified however, it is not clear if these are bona fide calcium channel subunits. Indeed, the first identified neuronal calcium channel y subunit stargazin has also been linked to AMPA receptor trafficking and pharmacology (Chen et al. 2000 Tomita et al. 2005). Hence, it remains unclear to what extent these subunits associate with the calcium channel complex in neurons. 

Xiao, W., Boroujerdi, A., Bennett, G. J., and Luo, Z. D. (2007). Chemotherapy-evoked painful peripheral neuropathy Analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit. Neuroscience 144, 714—720. 

Klugbauer N, Dai S, Specht V et al. (2000) A family of y-like calcium channel subunits. FEBS Lett 470 189-197... 

The disease is caused by a CAG expansion in the SCA6 gene at chromosome 19pl3, which codes for the aia-voltage-dependent calcium channel subunit (Zhuchenko et al., 1997). Six isoforms of this protein have been described. The CAG repeat is within the open reading frame and is predicted to encode Qn domains in... 

Calcium channels in the plasma membrane activated after receptor-mediated calcium release from intracellular stores. Diese channels are present in many cellular types and play pivotal roles in a multitude of cell functions. It was recently shown that Orai proteins are the pore-forming subunit of CRAC channels. They are activated by STIM proteins that sense the Ca2+ content of the endoplasmic reticulum. 

Functionally, the Dl-like receptors (Dl, D5) are coupled to the G protein Gas and thus can stimulate adenylyl cyclase. The D2-like receptors (D2, D3, and D4) couple to pertussis toxin sensitive G proteins (Gai/0), and consequently inhibit adenylyl cyclase activity. While the Dl-like receptors almost exclusively signal through Gas-mediated activation of adenylyl cyclase, the D2-like receptors have been reported to modulate the activity of a plethora of signaling molecules and pathways. Many of these actions are mediated through the G(3y subunit. Some of these molecules and pathways include the calcium channels, potassium channels, sodium-hydrogen exchanger, arachidonic acid release, and mitogen-activated protein kinase pathways. 

Protein kinase A (PKA) is a cyclic AMP-dependent protein kinase, a member of a family of protein kinases that are activated by binding of cAMP to their two regulatory subunits, which results in the release of two active catalytic subunits. Targets of PKA include L-type calcium channels (the relevant subunit and site of phosphorylation is still uncertain), phospholam-ban (the regulator of the sarcoplasmic calcium ATPase, SERCA) and key enzymes of glucose and lipid metabolism. 

Voltage-dependent Ca2+ channels are a family of multi-subunit complexes of five proteins responding to membrane depolarisation with channel opening allowing the influx of calcium into a cell. Voltage-dependent calcium channels are subdivided into three subfamilies the HVA DHP-sensitive L-type calcium channels, the HVA DHP-insensitive calcium channels and the LVA T-type calcium channels [2]. 

HVA calcium channels are biochemically hetero-oligomeric complexes of five proteins encoded by four gene families (Fig. 1) The ax subunits of 190-250 kDa contain the voltage-sensor, the selectivity filter, the ion-conducting pore, the binding sites for most calcium... 

Voltage-dependent Ca2+ Channels. Figure 2 Subunit composition of a HVA calcium channel. The selectivity filter of the channel is created by four glutamates (E). 

Vig M, DeHaven WI, Bird GS, Billingsley JM, Wang H, Rao PE, Hutchings AB, Jouvin MH, Putney JW, Kinet JP Defective mast cell effector functions in mice lacking the CRACMl pore subunit of store-operated calcium release-activated calcium channels. Nat Immunol 2008 9 89-96. 

Ikeda, S. R. and Dunlap, K., Voltage-dependent modulation of N-type calcium channels role of G-protein subunits, Adv. Second Messenger Phosphoprotein Res., 33, 131-151, 1999. 

Ten specific mammalian calcium channel subtypes have been identified based on the sequence of their membrane pore-forming oq subunit. As illustrated in Table 1, calcium channels may be individually identified by their oq subunit, or more commonly using a systematic nomenclature based on a gene subfamily (Cavl-Cav3) and the order of discovery of the oq subunit (e.g., Cavl.l-Cav 1.4) [7]. 

The pore-forming oq subunit alone is sufficient to form a functional calcium channel in the cell membrane [8]. However, high-voltage-activated calcium channels are hetero-oligomeric structures that may contain as many as three additional smaller subunits, labeled CX25 (itself a heterodimer), (5, and y. These three subunits associate in an auxiliary... 

---