Capacitative Ca2+ entry

Ca2+ can enter cells via voltage- or ligand-dependent channels and by capacitative entry. These three fundamental mechanisms of regulated calcium ion entry across the plasma membrane involve, respectively, voltage-dependent Ca2+ channels, ligand-gated Ca2+ channels and capacitative Ca2+ entry associated with phospholipase C-coupled receptors. 

Capacitative Ca2+ entry is the predominant mode of regulated Ca2+ entry in nonexcitable cells but it also occurs in a number of excitable cell types. This pathway of Ca2+ entry is usually associated with the activation of phospholipase C, which mediates the formation of IP3 (see Ch. 20). Intracellular application of IP3 mimics the ability of hormones and neurotransmitters to activate calcium ion entry, and activation of calcium ion entry by hormones and neurotransmitters can be blocked by intracellular application of low-molecular-weight heparin, which potently antagonizes IP3 binding to its receptor. There is considerable evidence for the presence of an IP3 receptor in the plasma membrane of some cells types. 1(1,3,4,5)P4, a product of IP3 phosphorylation, has been shown in some cells to augment this action of IP3 in activating PM calcium ion entry, but in others IP3 alone is clearly sufficient. 

While the molecular identity of the capacitative Ca2+ entry channel is not known, a candidate is a homolog of the Drosophila mutant trp. This photoreceptor mutant is incapable of maintaining a sustained photoreceptor potential. This phenotype could be mimicked by the calcium entry blocker lanthanum, and it was suggested that the related defect is a failure of Ca2+ entry. 

Taylor This whole argument about conformational coupling has to live with the fact that there is the DT40 cell line in which all InsP3 receptors have been knocked out, and capacitative Ca2+ entry is unaffected. 

Molecular candidates for capacitative and non-capacitative Ca2+ entry in smooth muscle... 

Kuriyama H, Kitamura K, Itoh T, Inoue R 1998 Physiological features of visceral smooth muscle cells, with special reference to receptors and ion channels. Physiol Rev 78 811—920 McDaniel SS, Platoshyn O, Wang J et al 2001 Capacitative Ca2+ entry in agonist-induced pulmonary vasoconstriction. Am J Physiol 280 L870-L880 Montell C 2001 Physiology, phylogeny, and functions of the TRP superfamily of cation channels. In Science s STKE, July, pi—17... 

The relative contributions of Ca2+ entry via CCE and second messenger-operated pathways to the Ca2+ signals evoked by physiological stimuli in the A7r5 vascular smooth muscle cell line. For simplicity, I refer to the second of these pathways as a non-capacitative Ca2+ entry (NCCE) pathway. 

Capacitative Ca2+ entry another role for InsP3 receptors... 

FIG. 2. The capacitative Ca2+ entry complex. The SR, with its resident Ca2+ pump (SERCA) and InsP3 receptors the plasma membrane, with the channels fl(-RAc) regulated by empty stores and mitochondria are all proposed to be intimately associated in this capacitative Ca2+ entry complex. Inevitably, as Ca2+ enters via Icrao I nslb receptors and SERCA will be transiently exposed to very high [Ca2+]c the implications are discussed in the text. 

FIG. 5. Only non-capacitative Ca2+ entry occurs during receptor activation. Cells were stimulated with vasopressin (30 nM for 300 s) under conditions where both, neither or only one of the Ca2+ entry pathways were blocked. The same scale applies to all four traces, with the origin shown on each by a thick line. (Results taken from Moneer Taylor [2002].) The cartoon indicates that reciprocal regulation of the two pathways may allow rapid switching between stimulation (contraction evoked by Ca2+ entering via NCCE) and recovery (relaxation evoked by Ca2+ entering via CCE)... 

Fagan KA, Mons N Cooper DMF 1998 Dependence of the Ca2+-mhibitable adenylyl cyclase of C6-2B glioma cells on capacitative Ca2+ entry. J Biol Chem 273 9297—9305 Fierro L, Parekh AB 2000 Substantial depletion of the intracellular Ca2+ stores is required for macroscopic activation of the Ca2+ release-activated Ca2+ current in rat basophilic leukaemia cells. J Physiol 522 247—257... 

Kiselyov K, Mignery GA, Zhu MX, Muallem S 1999 The N-terminal domain of the IP3 receptor gates store-operated hTrp3 channels. Mol Cell 4 423-429 Lee HC 2000 NAADP An emerging calcium signaling molecule. J Membr Biol 173 1 -8 Lin S, Fagan KA, Li K-X, Shaul PW, Cooper DMF, Rodman DM 2000 Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J Biol Chem 275 17979-17985... 

Parekh AB, Penner R 1997 Store depletion and calcium influx. Physiol Rev 77 901-930 Potocnik SJ, Hill MA 2001 Pharmacological evidence for capacitative Ca2+ entry in cannulated and pressurized skeletal muscle arterioles. Br J Pharmacol 134 247-256 Pozzan T, Rizzuto R, Volpe P, Meldolesi J 1994 Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74 595—636 Putney JW Jr, Broad LM, Braun FJ, Lievremont JP, Bird GS 2001 Mechanisms of capacitative calcium entry. J Cell Sci 114 2223—2229... 

Sweeney, M., Yu, Y., Platoshyn, O., Zhang, S., McDaniel, S. S. and Yuan, J. X., 2002, Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation. Am J Physiol Lung Cell Mol Physiol 283, L144—55. 

Varadi, A., Cirulli, V. and Rutter, G. A., 2004, Mitochondrial localization as a determinant of capacitative Ca2+ entry in HeLa cells. Cell Calcium 36, 499—508. 

Lomax, R. B. Herrero, C. J. et al. (1998). "Capacitative Ca2+ entry into Xenopus oocytes is sensitive to omega-conotoxins GVIA, MVIIA and MVIIC." Cell Calcium, 23(4), 229-39. 

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