Antisense knockdown of calcium-dependent K+ channels in developing cerebellar Purkinje neurons.
Normal developmental upregulation of K(Ca) channel activity in cultured rat cerebellar Purkinje neurons was selectively inhibited by antisense oligonucleotide sequence (3 microM) targeted against the rslo transcript. The knockdown was specific; delayed rectifier and apamin-sensitive K+ channel abundances in Purkinje neurons were not affected by rslo antisense. Sense oligonucleotides (3 microM), used as a control, had no effect on channel abundance. Quantitative morphometric analyses of anti-calbindin-labeled Purkinje neurons showed no differences between neurons in control, sense and antisense treatment groups, and confirmed that the presence of the added oligonucleotide in the sense and antisense treatment conditions had no discernable toxic effects on neuronal health, for which neurite outgrowth is a sensitive indicator. These results confirm the identification of the developmentally regulated K(Ca) channel as the product of the gene rslo in cerebellar Purkinje neurons.
Muller
Y L
YL
Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Reitstetter
R
R
Yool
A J
AJ
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D064026:Calbindins; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D064026:Calbindins; D016376:Oligonucleotides, Antisense; D024681:Potassium Channels, Calcium-Activated; D064030:S100 Calcium Binding Protein G; D001030:Apamin