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The Journal of Neuroscience, January 15, 1999, 19(2):684-691

Molecular Diversity of the Calcium Channel alpha 2delta Subunit

Norbert Klugbauer, Lubica Lacinová, Elsé Marais, Muriel Hobom, and Franz Hofmann

Institut für Pharmakologie und Toxikologie der Technischen Universität München, 80802 München, Germany

Sequence database searches with the alpha 2delta subunit as probe led to the identification of two new genes encoding proteins with the essential properties of this calcium channel subunit. Primary structure comparisons revealed that the novel alpha 2delta -2 and alpha 2delta -3 subunits share 55.6 and 30.3% identity with the alpha 2delta -1 subunit, respectively. The number of putative glycosylation sites and cysteine residues, hydropathicity profiles, and electrophysiological character of the alpha 2delta -3 subunit indicates that these proteins are functional calcium channel subunits. Coexpression of alpha 2delta -3 with alpha 1C and cardiac beta 2a or alpha 1E and beta 3 subunits shifted the voltage dependence of channel activation and inactivation in a hyperpolarizing direction and accelerated the kinetics of current inactivation. The kinetics of current activation were altered only when alpha 2delta -1 or alpha 2delta -3 was expressed with alpha 1C. The effects of alpha 2delta -3 on alpha 1C but not alpha 1E are indistinguishable from the effects of alpha 2delta -1. Using Northern blot analysis, it was shown that alpha 2delta -3 is expressed exclusively in brain, whereas alpha 2delta -2 is found in several tissues. In situ hybridization of mouse brain sections showed mRNA expression of alpha 2delta -1 and alpha 2delta -3 in the hippocampus, cerebellum, and cortex, with alpha 2delta -1 strongly detected in the olfactory bulb and alpha 2delta -3 in the caudate putamen.

Key words: alpha 2delta subunit; voltage-activated channel; calcium channel subunit; neuron; gene diversity; electrophysiology


Copyright © 1999 Society for Neuroscience  0270-6474/99/192684-08$05.00/0


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