Calcium channels P subunit

Petegem, F.V., Clark, K.A., Chatelain, F.C. and Minor, D.L. (2004) Structure of a complex between a voltagegated calcium channel P subunit and an a-subunit domain. Nature 429, 671-675. 

Valle, C., Troiani, A.R., Festucci, A., Pica-Mattoccia, L., Liberti, P., Wolstenholme, A., Francklow, K., Doenhoff, M.J. and Cioli, D. (2003) Sequence and level of endogenous expression of calcium channel P subunits in Schistosoma mansoni displaying different susceptibilities to praziquantel. Molecular and Biochemical Parasitology 130, 111-115. 

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... 

Zamponi, G.W., Bourinet, E., Nelson, D., Nargeot, J., Snutch, T.P. Crosstalk between G proteins and protein kinase C mediated by the calcium channel ai subunit, Nature 1997, 385, 442-446. 

Kohn, A.B., Anderson, P.A., Roberts-Misterly, J.M. and Greenberg, R.M. (2001) Schistosome calcium channel beta subunits unusual modulatory effects and potential role in the action of the antischistosomal drug praziquantel. Journal of Biological Chemistry 276, 36873-36876. 

Jeziorski, M.C., Greenberg, R.M. and Anderson, P.A.V. (2000b) Calcium channel (3 subunits differentially modulate recovery of the channel from inactivation. FEBS Fetters 483, 125-130. 

Pragnell, M., De Waard, M., Mori, Y., Tanabe, T., Snutch, T.P. and Campbell, K.P. (1994) Calcium channel (i-subunit binds to a conserved motif in the l-ll cytoplasmic linker of the oq-subunit. Nature 368, 67-70. 

Additional substantiating evidence that calcium channel auxiliary subunits might play pivotal roles in disease processes comes from the study of mouse models. Five murine diseases with similar phenotypes to Cav2.1 P/Q-type channel mutant-associated diseases have been linked to calcium channel auxiliary subunits (Tables 9-11). 

Calcium Channelopathies Involving P/Q-Type Calcium Channel ai Subunits. 53... 

There are also a number of murine models of P/Q-type channelopathies. Leaner, Tottering, rolling Nagoya, and Rocker mice all carry mutations in the Cav2.1 calcium channel ai subunit that result in either the substitution of individual amino acids or premature truncations of the channel protein. These mice tend to show an ataxic phenotype and, in some cases, absence seizures (Lorenzon et al. 1998 Mori et al. 2000 Noebels and Sidman 1979 Zwingman et al. 2001). In addition, several of these mutations cause cerebellar atrophy (Herrup and Wilczynski 1982). When introduced into recombinant channels, these mutations tend to reduce channel activity which is consistent with reduced P/Q-type currents in neurons isolated from these mouse lines. 

Potier B, Dutar P, Lamour Y (1993) Different effects of omega-conotoxin GVIA at excitatory and inhibitory synapses in rat CA1 hippocampal neurons. Brain Res 616 236 11 Pragnell M, De Waard M, Mori Y, Tanabe T, Snutch TP, Campbell KP (1994) Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit. Nature 368 67-70... 

Figure 7.11 Diagrammatic representation of the structure of calcium channel a, subunit from Drosophila. (From Hall, L.M. et al., in Molecular Action of Insecticides on Ion Channels, Clark, J.M., Ed., ACS Symposium Series 591, American Chemical Society, Washington, D.C., 1995, p. 162. With permission.)...

The p subunit of the calcium channel binds to the calcium channel Uj subunit at the intracellular loop between repeats I and II (Pragnell et al., 1994). The smooth muscle Uj subunit contains an insert in this region that is not present in the cardiac uj subunit (Biel et al., 1990). This insert may be necessary to interact efficiently with the P3 subunit of smooth muscle. The region of the p subunit that interacts with the loop I-II of the ttj subunit has been localized to a 30-amino acid domain between the amino acids 163 and 366 of the P3 subunit (De Waard et al., 1994). 

Jay, S.D., Sharp, A.H., Kahl, S.D., Vedvick, T.S., Harpold, M.M., and Campbell, K.P. (1991) Structural characterization of the dihydropyridine-sensitive calcium channel 2-subunit and the associated peptides. Journal of Biological Chemistry, 265 3287-3293. 

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Arikkath, J. and Campbell, K.P. (2003) Auxiliary subunits essential components of the voltage-gated calcium channel complex. Current Opinion in Neurobiology 13, 298-307. 

Dolphin, A.C. (2003) P subunits of voltage-gated calcium channels. Journal of Bioenergetics and Biomembranes 35, 599-620. 

Keywords calcium channel, L-type, P/Q-type, T-type, < subunit, 3 subunit, <. C subunit, y subunit,... 

Ayata C, Shimizu-Sasamata M, Lo EH, Noebels JL, Moskowitz MA (2000) Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alphalA subunit of P/Q type calcium channels. Neuroscience 95 639-645. 

Bourinet E, Soong TW, Sutton K, Slaymaker S, Mathews E, Monteil A, Zamponi GW, Nargeot J, Snutch TP (1999) Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels. Nat Neurosci 2 407 115. 

Restituito S, Thompson RM, Eliet J, Raike RS, Riedl M, Chamet P, Gomez CM (2000) The polyglutamine expansion in spinocerebellar ataxia type 6 causes a beta subunit-specific enhanced activation of P/Q-type calcium channels in Xenopus oocytes. J Neurosci 20 6394—6403. 

Monnier, N., Procaccio, V., Stieglitz, P., and Lunardi, J. (1997). Malignant -Hyperthermia Susceptibility Is Associated With Mutation of the alpha 1-Subunit of the Human Dihydropyridine-Sensitive L-Type Voltage-Dependent Calcium-Channel Receptor in Skeletal Muscle. Am. J. Hum. Genet. 60 1316—25. 

Bian, F., Li, Z., Offord, J., Davis, M. D., McCormick, J., Taylor, C. P, et al. (2006) Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord an ex vivo autoradiographic study... 

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