tipE regulates Na+-dependent repetitive firing in Drosophila neurons.
The tipE gene, originally identified by a temperature-sensitive paralytic mutation in Drosophila, encodes a transmembrane protein that dramatically influences sodium channel expression in Xenopus oocytes. There is evidence that tipE also modulates sodium channel expression in the fly; however, its role in regulating neuronal excitability remains unclear. Here we report that the majority of neurons in both wild-type and tipE mutant (tipE-) embryo cultures fire sodium-dependent action potentials in response to depolarizing current injection. However, the percentage of tipE- neurons capable of firing repetitively during a sustained depolarization is significantly reduced. Expression of a tipE+ transgene, in tipE- neurons, restores repetitive firing to wild-type levels. Analysis of underlying currents reveals a slower rate of repolarization-dependent recovery of voltage-gated sodium currents during repeated activation in tipE- neurons. This phenotype is also rescued by expression of the tipE+ transgene. These data demonstrate that tipE regulates sodium-dependent repetitive firing and recovery of sodium currents during repeated activation. Furthermore, the duration of the interstimulus interval necessary to fire a second full-sized action potential is significantly longer in single- versus multiple-spiking transgenic neurons, suggesting that a slow rate of recovery of sodium currents contributes to the decrease in repetitive firing in tipE- neurons.
Hodges
Dianne D
DD
Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, California 92697-1280, USA.
Lee
Daewoo
D
Preston
Charles F
CF
Boswell
Kevin
K
Hall
Linda M
LM
O'Dowd
Diane K
DK
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D004330:Drosophila; D029721:Drosophila Proteins; D015870:Gene Expression / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000502:physiology
D029721:Drosophila Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; C095833:TipE protein, Drosophila; D012964:Sodium