Article
Alternate splicing in the cytosolic II-III loop and the carboxy terminus of human E-type voltage-gated Ca(2+) channels: electrophysiological characterization of isoforms.
Institute of Neurophysiology, University of Cologne, Robert-Koch-Strasse 39, D-50931 Cologne, Germany.
Molecular and Cellular Neuroscience (impact factor:
3.66).
11/2002;
21(2):352-65.
Source: PubMed
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Citations (0)
- Cited In (2)
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Article: Atypical properties of a conventional calcium channel beta subunit from the platyhelminth Schistosoma mansoni.
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ABSTRACT: The function of voltage-gated calcium (Cav) channels greatly depends on coupling to cytoplasmic accessory beta subunits, which not only promote surface expression, but also modulate gating and kinetic properties of the alpha1 subunit. Schistosomes, parasitic platyhelminths that cause schistosomiasis, express two beta subunit subtypes: a structurally conventional beta subunit and a variant beta subunit with unusual functional properties. We have previously characterized the functional properties of the variant Cavbeta subunit. Here, we focus on the modulatory phenotype of the conventional Cavbeta subunit (SmCavbeta) using the human Cav2.3 channel as the substrate for SmCavbeta and the whole-cell patch-clamp technique. The conventional Schistosoma mansoni Cavbeta subunit markedly increases Cav2.3 currents, slows macroscopic inactivation and shifts steady state inactivation in the hyperpolarizing direction. However, currents produced by Cav2.3 in the presence of SmCavbeta run-down to approximately 75% of their initial amplitudes within two minutes of establishing the whole-cell configuration. This suppressive effect was independent of Ca2+, but dependent on intracellular Mg2+-ATP. Additional experiments revealed that SmCavbeta lends the Cav2.3/SmCavbeta complex sensitivity to Na+ ions. A mutant version of the Cavbeta subunit lacking the first forty-six amino acids, including a string of twenty-two acidic residues, no longer conferred sensitivity to intracellular Mg2+-ATP and Na+ ions, while continuing to show wild type modulation of current amplitude and inactivation of Cav2.3. The data presented in this article provide insights into novel mechanisms employed by platyhelminth Cavbeta subunits to modulate voltage-gated Ca2+ currents that indicate interactions between the Ca2+ channel complex and chelated forms of ATP as well as Na+ ions. These results have potentially important implications for understanding previously unknown mechanisms by which platyhelminths and perhaps other organisms modulate Ca2+ currents in excitable cells.BMC Physiology 02/2008; 8:6. -
Article: International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels.
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ABSTRACT: The family of voltage-gated calcium channels serves as the key transducers of cell surface membrane potential changes into local intracellular calcium transients that initiate many different physiological events. There are 10 members of the voltage-gated calcium channel family that have been characterized in mammals, and they serve distinct roles in cellular signal transduction. This article presents the molecular relationships and physiological functions of these calcium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties.Pharmacological Reviews 01/2006; 57(4):411-25. · 20.23 Impact Factor
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Keywords
alpha1E
charge carrier
definition resistant
dendritic integration
endocrine Ca(v)2.3 splice variants
heterogeneous group
inactivation time course
individual variants
ion-conducting subunit
L-
major differences
splice variation
tested biophysical properties
typical