Functional expression of a rapidly inactivating neuronal calcium channel

• Published in: Nature (London) 1993-06, Vol.363 (6428), p.455-458
• Main Authors: Ellinor, Patrick T, Zhang, Ji-Fang, Randall, Andrew D, Zhou, Mei, Schwarz, Thomas L, Tsien, Richard W, Horne, William A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain; Calcium; Calcium channels; Calcium Channels - drug effects; Calcium Channels - genetics; Calcium Channels - metabolism; Central nervous system; Cerebral Cortex - cytology; Cloning, Molecular; Dihydropyridines - antagonists & inhibitors; Electrophysiology; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; In Vitro Techniques; letter; Membrane Potentials; Mollusk Venoms - pharmacology; multidisciplinary; Neurons; Neurons - metabolism; Nickel - pharmacology; omega-Agatoxin IVA; omega-Conotoxin GVIA; omega-Conotoxins; Oocytes; Peptides - pharmacology; Peptides, Cyclic - pharmacology; Rabbits; Rats; Rodents; Science; Science (multidisciplinary); Skates (Fish); Spider Venoms - pharmacology; Vertebrates: nervous system and sense organs; Xenopus
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/363455a0

DIVERSE types of calcium channels in vertebrate neurons are important in linking electrical activity to transmitter release, gene expression and modulation of membrane excitability 1 . Four classes of Ca 2+ channels (T, N, L and P-type) have been distinguished 2–6 on the basis of their electrophysiological and pharmacological properties. Most of the recently cloned Ca 2+ channels 7–16 fit within this functional classification. But one major branch of the Ca 2+ channel gene family, including BII (ref. 15) and doe-1 (ref. 16), has not been functionally characterized. We report here the expression of doe-1 and show that it is a high-voltage-activated (HVA) Ca 2+ channel that inactivates more rapidly than previously expressed calcium channels. Unlike L-type or P-type channels, doe-1 is not blocked by dihydropyridine antagonists or the peptide toxin ω-Aga-IVA, respectively. In contrast to a previously cloned N-type channel 14 , doe-1 block by ω-CTx-GVIA requires microm-olar toxin and is readily reversible. Unlike most HVA channels, doe-1 also shows unusual sensitivity to block by Ni 2+ . Thus, doe-1 is an HVA Ca 2+ channel with novel functional properties. We have identified a Ca 2+ channel current in rat cerebellar granule neurons that resembles doe-1 in many kinetic and pharmacological features.