Drosophila Cacophony Channels: a Major Mediator of Neuronal Ca2+ Currents and a Trigger for K+ Channel Homeostatic Regulation

Overview

Journal J Neurosci

Specialty Neurology

Date 2007 Feb 3

PMID 17267561

Citations 40

Authors

I-Feng Peng

Chun-Fang Wu

Affiliations

Soon will be listed here.

Abstract

The cacophony (cac) locus in Drosophila encodes a Ca2+ channel alpha subunit, but little is known about properties of cac-mediated currents and functional consequences of cac mutations in central neurons. We found that, in Drosophila cultured neurons, Ca2+ currents were mediated predominantly by the cac channels. The cac channels contribute to low- and high-threshold, fast- and slow-inactivating types of Ca2+ currents, take part in membrane depolarization, and strongly activate Ca2+-activated K+ current [I(K(Ca))]. In cac neurons, unexpectedly, voltage-activated transient K+ current I(A) is upregulated to a level that matches I(K(Ca)) reduction, implicating a homeostatic regulation that was mimicked by chronic pharmacological blockade of Ca2+ currents in wild-type neurons. Among K+ channel transcripts, Shaker mRNA levels were preferentially increased in cac flies. However, Ca2+ current expression levels remained unaltered in several K+ channel mutants, illustrating a key role of cac in developmental regulation of Drosophila neuronal excitability.

Citing Articles

Ca channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity.

Medeiros A, Gratz S, Delgado A, Ritt J, OConnor-Giles K Elife. 2024; 12.

PMID: 39291956 PMC: 11410372. DOI: 10.7554/eLife.88412.

Ca channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity.

Medeiros A, Gratz S, Delgado A, Ritt J, OConnor-Giles K bioRxiv. 2023; .

PMID: 37034654 PMC: 10081318. DOI: 10.1101/2023.04.02.535290.

Seizure Phenotype and Underlying Cellular Defects in Knock-In Models of DS (R1648C) and GEFS+ (R1648H) Epilepsy.

Roemmich A, Vu T, Lukacsovich T, Hawkins C, Schutte S, ODowd D eNeuro. 2021; 8(5).

PMID: 34475263 PMC: 8454921. DOI: 10.1523/ENEURO.0002-21.2021.

Restoration of Olfactory Memory in Overexpressing Human Alzheimer's Disease Associated Tau by Manipulation of L-Type Ca Channels.

Higham J, Hidalgo S, Buhl E, Hodge J Front Cell Neurosci. 2019; 13:409.

PMID: 31551716 PMC: 6746915. DOI: 10.3389/fncel.2019.00409.

Maintenance of homeostatic plasticity at the neuromuscular synapse requires continuous IP-directed signaling.

James T, Zwiefelhofer D, Frank C Elife. 2019; 8.

PMID: 31180325 PMC: 6557630. DOI: 10.7554/eLife.39643.

References

Spitzer N . New dimensions of neuronal plasticity. Nat Neurosci. 1999; 2(6):489-91. DOI: 10.1038/9132. View

Gielow M, Gu G, Singh S . Resolution and pharmacological analysis of the voltage-dependent calcium channels of Drosophila larval muscles. J Neurosci. 1995; 15(9):6085-93. PMC: 6577691. View

Berke B, Lee J, Peng I, Wu C . Sub-cellular Ca2+ dynamics affected by voltage- and Ca2+-gated K+ channels: Regulation of the soma-growth cone disparity and the quiescent state in Drosophila neurons. Neuroscience. 2006; 142(3):629-44. DOI: 10.1016/j.neuroscience.2006.06.051. View

Smith L, Wang X, Peixoto A, Neumann E, Hall L, Hall J . A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects. J Neurosci. 1996; 16(24):7868-79. PMC: 6579206. View

Singh S, Wu C . Complete separation of four potassium currents in Drosophila. Neuron. 1989; 2(4):1325-9. DOI: 10.1016/0896-6273(89)90070-6. View

Poulain C, Ferrus A, Mallart A . Modulation of type A K+ current in Drosophila larval muscle by internal Ca2+; effects of the overexpression of frequenin. Pflugers Arch. 1994; 427(1-2):71-9. DOI: 10.1007/BF00585944. View

Hell J, Westenbroek R, Elliott E, Catterall W . Differential phosphorylation, localization, and function of distinct alpha 1 subunits of neuronal calcium channels. Two size forms for class B, C, and D alpha 1 subunits with different COOH-termini. Ann N Y Acad Sci. 1994; 747:282-93. View

Llinas R, Steinberg I, Walton K . Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse. Biophys J. 1981; 33(3):323-51. PMC: 1327434. DOI: 10.1016/S0006-3495(81)84899-0. View

Zhao M, Wu C . Alterations in frequency coding and activity dependence of excitability in cultured neurons of Drosophila memory mutants. J Neurosci. 1997; 17(6):2187-99. PMC: 6793766. View

10.

Berke B, Wu C . Regional calcium regulation within cultured Drosophila neurons: effects of altered cAMP metabolism by the learning mutations dunce and rutabaga. J Neurosci. 2002; 22(11):4437-47. PMC: 6758795. DOI: 20026300. View

11.

Moreno Davila H . Molecular and functional diversity of voltage-gated calcium channels. Ann N Y Acad Sci. 1999; 868:102-17. DOI: 10.1111/j.1749-6632.1999.tb11281.x. View

12.

MacLean J, Zhang Y, Johnson B, Harris-Warrick R . Activity-independent homeostasis in rhythmically active neurons. Neuron. 2003; 37(1):109-20. DOI: 10.1016/s0896-6273(02)01104-2. View

13.

Ertel E, Campbell K, Harpold M, Hofmann F, Mori Y, Perez-Reyes E . Nomenclature of voltage-gated calcium channels. Neuron. 2000; 25(3):533-5. DOI: 10.1016/s0896-6273(00)81057-0. View

14.

Peng I, Wu C . Differential contributions of Shaker and Shab K+ currents to neuronal firing patterns in Drosophila. J Neurophysiol. 2006; 97(1):780-94. DOI: 10.1152/jn.01012.2006. View

15.

Engel J, Wu C . Genetic dissection of functional contributions of specific potassium channel subunits in habituation of an escape circuit in Drosophila. J Neurosci. 1998; 18(6):2254-67. PMC: 6792913. View

16.

Wei A, Covarrubias M, Butler A, Baker K, Pak M, Salkoff L . K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse. Science. 1990; 248(4955):599-603. DOI: 10.1126/science.2333511. View

17.

Zhong Y, Wu C . Differential modulation of potassium currents by cAMP and its long-term and short-term effects: dunce and rutabaga mutants of Drosophila. J Neurogenet. 1993; 9(1):15-27. DOI: 10.3109/01677069309167273. View

18.

Gola M, Crest M . Colocalization of active KCa channels and Ca2+ channels within Ca2+ domains in helix neurons. Neuron. 1993; 10(4):689-99. DOI: 10.1016/0896-6273(93)90170-v. View

19.

Komatsu A, Singh S, Rathe P, Wu C . Mutational and gene dosage analysis of calcium-activated potassium channels in Drosophila: correlation of micro- and macroscopic currents. Neuron. 1990; 4(2):313-21. DOI: 10.1016/0896-6273(90)90105-o. View

20.

Leung H, Byerly L . Characterization of single calcium channels in Drosophila embryonic nerve and muscle cells. J Neurosci. 1991; 11(10):3047-59. PMC: 6575429. View