Knockdown of a Cyclic Nucleotide-Gated Ion Channel Impairs Locomotor Activity and Recovery From Hypoxia in Adult

Overview

Journal Front Physiol

Date 2022 May 9

PMID 35530504

Authors

Shuang Qiu

Chengfeng Xiao

R Meldrum Robertson

Affiliations

Soon will be listed here.

Abstract

Cyclic guanosine monophosphate (cGMP) modulates the speed of recovery from anoxia in adult and mediates hypoxia-related behaviors in larvae. Cyclic nucleotide-gated channels (CNG) and cGMP-activated protein kinase (PKG) are two cGMP downstream targets. PKG is involved in behavioral tolerance to hypoxia and anoxia in adults, however little is known about a role for CNG channels. We used a CNGL (CNG-like) mutant with reduced transcripts to investigate the contribution of CNGL to the hypoxia response. CNGL mutants had reduced locomotor activity under normoxia. A shorter distance travelled in a standard locomotor assay was due to a slower walking speed and more frequent stops. In control flies, hypoxia immediately reduced path length per minute. Flies took 30-40 min in normoxia for >90% recovery of path length per minute from 15 min hypoxia. CNGL mutants had impaired recovery from hypoxia; 40 min for ∼10% recovery of walking speed. The effects of CNGL mutation on locomotor activity and recovery from hypoxia were recapitulated by pan-neuronal knockdown. Genetic manipulation to increase cGMP in the CNGL mutants increased locomotor activity under normoxia and eliminated the impairment of recovery from hypoxia. We conclude that CNGL channels and cGMP signaling are involved in the control of locomotor activity and the hypoxic response of adult .

References

Callier V, Hand S, Campbell J, Biddulph T, Harrison J . Developmental changes in hypoxic exposure and responses to anoxia in Drosophila melanogaster. J Exp Biol. 2015; 218(Pt 18):2927-34. DOI: 10.1242/jeb.125849. View

Grima B, Chelot E, Xia R, Rouyer F . Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain. Nature. 2004; 431(7010):869-73. DOI: 10.1038/nature02935. View

Smith R, Louis C, Kruszyna R, Kruszyna H . Acute neurotoxicity of sodium azide and nitric oxide. Fundam Appl Toxicol. 1991; 17(1):120-7. DOI: 10.1016/0272-0590(91)90244-x. View

Picton L, Sillar K, Zhang H . Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in Excitatory Interneurons. Curr Biol. 2018; 28(24):3911-3923.e2. PMC: 6303192. DOI: 10.1016/j.cub.2018.10.048. View

Selvatici R, Previati M, Marino S, Marani L, Falzarano S, Lanzoni I . Sodium azide induced neuronal damage in vitro: evidence for non-apoptotic cell death. Neurochem Res. 2008; 34(5):909-16. DOI: 10.1007/s11064-008-9852-0. View

Haddad G . Tolerance to low O2: lessons from invertebrate genetic models. Exp Physiol. 2006; 91(2):277-82. DOI: 10.1113/expphysiol.2005.030767. View

Day J, Dow J, Houslay M, Davies S . Cyclic nucleotide phosphodiesterases in Drosophila melanogaster. Biochem J. 2005; 388(Pt 1):333-42. PMC: 1186723. DOI: 10.1042/BJ20050057. View

Cummins T, Donnelly D, Haddad G . Effect of metabolic inhibition on the excitability of isolated hippocampal CA1 neurons: developmental aspects. J Neurophysiol. 1991; 66(5):1471-82. DOI: 10.1152/jn.1991.66.5.1471. View

Morton D . Atypical soluble guanylyl cyclases in Drosophila can function as molecular oxygen sensors. J Biol Chem. 2004; 279(49):50651-3. DOI: 10.1074/jbc.C400461200. View

10.

Campbell J, Andersen M, Overgaard J, Harrison J . Paralytic hypo-energetic state facilitates anoxia tolerance despite ionic imbalance in adult . J Exp Biol. 2018; 221(Pt 12). DOI: 10.1242/jeb.177147. View

11.

Gray J, Karow D, Lu H, Chang A, Chang J, Ellis R . Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature. 2004; 430(6997):317-22. DOI: 10.1038/nature02714. View

12.

Dawson-Scully K, Bukvic D, Chakaborty-Chatterjee M, Ferreira R, Milton S, Sokolowski M . Controlling anoxic tolerance in adult Drosophila via the cGMP-PKG pathway. J Exp Biol. 2010; 213(Pt 14):2410-6. PMC: 2892421. DOI: 10.1242/jeb.041319. View

13.

Hammond S, Bernstein E, Beach D, Hannon G . An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. 2000; 404(6775):293-6. DOI: 10.1038/35005107. View

14.

Varming T, Drejer J, Frandsen A, Schousboe A . Characterization of a chemical anoxia model in cerebellar granule neurons using sodium azide: protection by nifedipine and MK-801. J Neurosci Res. 1996; 44(1):40-6. DOI: 10.1002/(SICI)1097-4547(19960401)44:1<40::AID-JNR5>3.0.CO;2-I. View

15.

Chang A, Chronis N, Karow D, Marletta M, Bargmann C . A distributed chemosensory circuit for oxygen preference in C. elegans. PLoS Biol. 2006; 4(9):e274. PMC: 1540710. DOI: 10.1371/journal.pbio.0040274. View

16.

Bradley J, Zhang Y, Bakin R, Lester H, Ronnett G, Zinn K . Functional expression of the heteromeric "olfactory" cyclic nucleotide-gated channel in the hippocampus: a potential effector of synaptic plasticity in brain neurons. J Neurosci. 1997; 17(6):1993-2005. PMC: 6793760. View

17.

Sepp K, Schulte J, Auld V . Peripheral glia direct axon guidance across the CNS/PNS transition zone. Dev Biol. 2002; 238(1):47-63. DOI: 10.1006/dbio.2001.0411. View

18.

Luo L, Liao Y, Jan L, Jan Y . Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev. 1994; 8(15):1787-802. DOI: 10.1101/gad.8.15.1787. View

19.

Dimitroff B, Howe K, Watson A, Campion B, Lee H, Zhao N . Diet and energy-sensing inputs affect TorC1-mediated axon misrouting but not TorC2-directed synapse growth in a Drosophila model of tuberous sclerosis. PLoS One. 2012; 7(2):e30722. PMC: 3272037. DOI: 10.1371/journal.pone.0030722. View

20.

Metaxakis A, Oehler S, Klinakis A, Savakis C . Minos as a genetic and genomic tool in Drosophila melanogaster. Genetics. 2005; 171(2):571-81. PMC: 1456772. DOI: 10.1534/genetics.105.041848. View