Modulation of dihydropyridine-sensitive calcium channels indrosophila by a cAMP-mediated pathway

✍ Scribed by Bhattacharya, Anindya ;Gu, Gang-Guo ;Singh, Satpal

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 169 KB
• Volume: 39
• Category: Article
• ISSN: 0022-3034
• DOI: 10.1002/(sici)1097-4695(19990615)39:4<491::aid-neu3>3.0.co;2-6

✦ Synopsis

Drosophila has proved to be a valuable system for studying the structure and function of ion channels. However, relatively little is known about the regulation of ion channels, particularly that of Ca 2؉ channels, in Drosophila. Physiological and pharmacological differences between invertebrate and mammalian L-type Ca 2؉ channels raise questions on the extent of conservation of Ca 2؉ channel modulatory pathways. We have examined the role of cyclic adenosine monophosphate (cAMP) cascade in modulating the dihydropyridine (DHP)-sensitive Ca 2؉ channels in the larval muscles of Drosophila, using mutations and drugs that disrupt specific steps in this pathway. The L-type (DHPsensitive) Ca 2؉ channel current was increased in the dunce mutants, which have high cAMP concentration owing to cAMP-specific phosphodiesterase (PDE) disruption. The current was decreased in the rutabaga mutants, where adenylyl cyclase (AC) activity is altered thereby decreasing the cAMP concentration. The dunce effect was mimicked by 8-Br-cAMP, a cAMP analog, and IBMX, a PDE inhibitor. The rutabaga effect was rescued by forskolin, an AC activator. H-89, an inhibitor of protein kinase-A (PKA), reduced the current and inhibited the effect of 8-Br-cAMP. The data suggest modulation of L-type Ca 2؉ channels of Drosophila via a cAMP-PKA mediated pathway. While there are differences in L-type channels, as well as in components of cAMP cascade, between Drosophila and vertebrates, main features of the modulatory pathway have been conserved. The data also raise questions on the likely role of DHP-sensitive Ca 2؉ channel modulation in synaptic plasticity, and learning and memory, processes disrupted by the dnc and the rut mutations.