The Roles of the Subunits in the Function of the Calcium Channel

• Published in: Science (American Association for the Advancement of Science) 1991-09, Vol.253 (5027), p.1553-1557
• Main Authors: Singer, Dafna, Biel, Martin, Lotan, Ilana, Flockerzi, Veit, Hofmann, Franz, Dascal, Nathan
• Format: Article
• Language: English
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Barium - pharmacology; Barium Compounds; Cadmium - pharmacology; Cadmium Chloride; Calcium channels; Calcium Channels - drug effects; Calcium Channels - genetics; Calcium Channels - physiology; Cellular biology; Chlorides; Complementary DNA; Complementary RNA; Dihydropyridine; Electric current; Electric potential; Heart - physiology; Kinetics; Macromolecular Substances; Membrane Potentials - drug effects; Messenger RNA; Oocytes; Oocytes - physiology; RNA, Messenger - genetics; Skeletal muscle; Smooth muscle; Xenopus
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1716787

Dihydropyridine-sensitive voltage-dependent L-type calcium channels are critical to excitation-secretion and excitation-contraction coupling. The channel molecule is a complex of the main, pore-forming subunit $\alpha_1$ and four additional subunits: $\alpha_2$, δ,β, and γ ($\alpha_2$ and δ are encoded by a single messenger RNA). The $\alpha_1$ subunit messenger RNA alone directs expression of functional calcium channels in Xenopus oocytes, and coexpression of the $\alpha_2/\delta$ and β subunits enhances the amplitude of the current. The $\alpha_2$, δ, and γ subunits also have pronounced effects on its macroscopic characteristics, such as kinetics, voltage dependence of activation and inactivation, and enhancement by a dihydropyridine agonist. In some cases, specific modulatory functions can be assigned to individual subunits, whereas in other cases the different subunits appear to act in concert to modulate the properties of the channel.