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Calcium Channel Expression
Published by Anonymous on 2007/9/27 (1685 reads)
1: J Bioenerg Biomembr. 2003 Dec;35(6):639-47.


Calcium channel alpha2delta subunits: differential expression, function, and drug binding.

Klugbauer N, Marais E, Hofmann F.

Institut für Pharmakologie und Toxikologie, Technische Universität München, Bíedersteiner Str. 29, 80802 München, Germany. klugbauer@ipt.med.tu-muenchen.de

Voltage-activated calcium channels are transmembrane proteins that act as transducers of electrical signals into numerous intracellular activities. On the basis of their electrophysiological properties they are classified as high- and low-voltage-activated calcium channels. High-voltage-activated calcium channels are heterooligomeric proteins consisting of a pore-forming alpha1 subunit and auxiliary alpha2delta, beta, and--in some tissues--gamma subunits. Auxiliary subunits support the membrane trafficking of the alpha1 subunit and modulate the kinetic properties of the channel. In particular, the alpha2delta subunit has been shown to modify the biophysical and pharmacological properties of the alpha1 subunit. The alpha2delta subunit is posttranslationally cleaved to form disulfide-linked alpha2 and, delta proteins, both of which are heavily glycosylated. Recently it was shown that at least four genes encode for alpha2delta subunits which are expressed in a tissue-specific manner. Their biophysical properties were characterized in coexpression studies with high- and low-voltage-activated calcium channels. Mutations in the gene encoding alpha2delta-2 have been found to underlie the ducky phenotype. This mouse mutant is a model for absence epilepsy and is characterized by spike wave seizures and cerebellar ataxia. Alpha2delta subunits can also support pharmacological interactions with drugs that are used for the treatment of epilepsy and neuropathic pain.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15000524 [PubMed - indexed for MEDLINE]

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2: Basic Res Cardiol. 2002;97 Suppl 1:I4-10.


Expression of the L-type calcium channel in human heart failure.

Hersel J, Jung S, Mohacsi P, Hullin R.

Herzzentrum Leipzig, Klinik für Herzchirurgie, Russenstrasse 19, 04289 Leipzig, Germany.

L-type calcium channels play an important role in excitation-contraction coupling. After cardiomyocyte depolarization L-type calcium channels open and Ca2+ ions enter the cell. These small Ca2+ inward currents trigger calcium release from the junctional sarcoplasmic reticulum, a process called calcium-induced calcium release. Subsequently, the cytosolic Ca2+ concentration rises rapidly to levels that initiate contraction. In heart failure calcium-induced calcium release is disturbed, and in this review we focus on the L-type calcium channel and its contribution to this defective excitation-contraction coupling.

Publication Types:
Review

PMID: 12479227 [PubMed - indexed for MEDLINE]

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3: Ann N Y Acad Sci. 2002 Oct;971:127-34.


Regulation of voltage-dependent sodium channel expression in adrenal chromaffin cells: involvement of multiple calcium signaling pathways.

Kobayashi H, Shiraishi S, Yanagita T, Yokoo H, Yamamoto R, Minami S, Saitoh T, Wada A.

Department of Pharmacology, Miyazaki Medical College, Miyazaki 889-1692, Japan. hkobayas@post.miyazaki-med.ac.jp

The density and electrical activity of cell surface voltage-dependent Na(+) channels are key determinants regulating the neuronal plasticity including development, differentiation, and regeneration. Abnormalities of Na(+) channels are associated with various neurological diseases. In this paper, we review the regulatory mechanisms of cell surface Na(+) channel expression mediated by Ca(2+) signaling pathways in cultured bovine adrenal chromaffin cells. Sustained, but not transient, elevation of intracellular Ca(2+) concentration reduced the number of cell surface Na(+) channels. The reduction of Na(+) channels was suppressed by an inhibitor of calpain, a Ca(2+)-dependent protease, and by an inhibitor of protein kinase C (PKC). The activation of conventional PKC-alpha and novel PKC-epsilon reduced cell surface Na(+) channels by the acceleration of internalization of the channels and by the increased degradation of Na(+) channel alpha-subunit mRNA, respectively. On the contrary, the activation of PKC-epsilon increased Na(+) channel beta(1)-subunit mRNA level. The inhibition of calcineurin, a Ca(2+)/calmodulin-dependent protein phosphatase 2B, by immunosuppressants upregulated cell surface Na(+) channels by both stimulating externalization and inhibiting internalization of the channels without changing Na(+) channel alpha- and beta(1)-subunit mRNA levels. Thus, the signal transduction pathways mediated by intracellular Ca(2+) modulate cell surface Na(+) channel expression via multiple Ca(2+)-dependent events, and the changes in the intracellular vesicular trafficking are the important mechanisms in the regulation of Na(+) channel expression.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12438102 [PubMed - indexed for MEDLINE]

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4: J Cardiovasc Pharmacol. 2000;35(3 Suppl 1):S31-40.


New insights into the therapeutic mechanism of action of calcium channel blockers in salt-dependent hypertension: their interaction with endothelin gene expression.

Godfraind T.

Laboratoire de Pharmacologie, Faculté de Médecine, Université Catholique de Louvain, Brussels, Belgium.

It appears that the beneficial action of calcium channel blockers (CCBs) in hypertension may be related to short-term and long-term effects. This paper summarises pharmacological studies aiming to characterise those effects. The primary consequence of the short-term effects is the decrease of blood pressure related to a selective interaction of CCBs with calcium channels in hypertensive vessels. The long-term effects may additionally control the disease through prevention of end organ damage, accompanying the interaction of CCBs with the pathways, leading to the re-expression of embryonic genes and to the overactivation of type I collagen gene, which are amplified by a high-salt diet. ET-1 and tumour growth factor beta-1 could be among the main factors activating those pathways. The processes leading to overexpression of those factors and to tissue remodelling may be controlled by lacidipine, independent of the reduction of blood pressure.

Publication Types:
Review

PMID: 11347859 [PubMed - indexed for MEDLINE]

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5: J Neurobiol. 1998 Oct;37(1):146-57.


Intracellular calcium regulation of channel and receptor expression in the plasmalemma: potential sites of sensitivity along the pathways linking transcription, translation, and insertion.

Barish ME.

Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.

Nervous system development is "activity dependent"--activation of neurons controls their development, which controls their activation patterns, which will then influence their further development, and so on. A critical issue is thus the regulation of channel and receptor expression. For nerve cells, the presence of specialized Ca2+-permeable channels in the surface membrane provides a direct link between electrical activity and the intracellular Ca2+ ion concentration ([Ca2+]i), and in many instances [Ca2+]i is thought to link membrane activation and internal biosynthesis. In this context, Ca2+-permeable channels function as "activity sensors," transducing membrane activation by admitting Ca2+ rapidly, locally, and proportionately. In this review, I consider the potential of [Ca2+]i to regulate channel and receptor expression. I emphasize mechanisms by which the Ca2+ concentration of the cytosol and/or the Ca2+ concentrations of membrane-delimited Ca2+ sequestering organelles may influence biosynthetic processes. Here, I use "expression" in the most general sense of referring to the number and location of functional channels and receptors in the plasmalemma; regulation of expression is not limited to transcriptional regulation, but further encompasses translational and posttranslational processes. At the core is the notion of regulation by patterned oscillations in cytosolic [Ca2+], and, in a synchronous or contrapuntal manner, filling and depletion of a series of Ca2+-sequestering organelles--nuclear envelope, endoplasmic reticulum, Golgi, trans-Golgi network, and secretory vesicles--that all also have critical roles in biosynthesis of membrane proteins. These structures provide both an internal Ca2+ regulation and distribution system, and a scaffold for synthesis, targeting, and insertion of channels and receptors.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 9777738 [PubMed - indexed for MEDLINE]

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6: J Bioenerg Biomembr. 1998 Aug;30(4):409-18.


Differential expression and association of calcium channel subunits in development and disease.

McEnery MW, Vance CL, Begg CM, Lee WL, Choi Y, Dubel SJ.

Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4970, USA.

Voltage-gated calcium channels (VDCC) are essential to neuronal maturation and differentiation. It is believed that important signaling information is encoded by VDCC-mediated calcium influx that has both spatial and temporal components. VDCC are multimeric complexes comprised of a pore-forming alpha1 subunit and auxiliary beta and alpha2/delta subunits. Changes in the fractional contribution of distinct calcium conductances to the total calcium current have been noted in developing and differentiating neurons. These changes are anticipated to reflect the differential expression and localization of the pore-forming alpha1 subunits. However, as in vitro studies have established that beta regulates the channel properties and targeting of alpha1, attention has been directed toward the developmental expression and assembly of beta isoforms. Recently, changes in the beta component of the omega-conotoxin GVIA (CTX)-sensitive N-type VDCC have indicated differential assembly of alpha1B with beta in postnatal rat brain. In addition, unique properties of beta4 have been noted with respect to its temporal pattern of expression and incorporation into N-type VDCC complexes. Therefore, the expression and assembly of specific alpha1/beta complexes may reflect an elaborate cellular strategy for regulating VDCC diversity. The importance of these developmental findings is bolstered by a recent study which identified mutations in the beta4 as the molecular defect in the mutant epileptic mouse (lethargic; lh/lh). As beta4 is normally expressed in both forebrain and cerebellum, one may consider the impact of the loss of beta4 upon VDCC assembly and activity. The importance of the beta1b and beta4 isoforms to calcium channel maturation and assembly is discussed.

Publication Types:
Comparative Study
Review

PMID: 9758336 [PubMed - indexed for MEDLINE]
 

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