A cytoplasmic cell cycle controls the activity of a K+ channel in pre-implantation mouse embryos.
We previously have reported that the activity of a 240 pS K+ channel varies during the cell cycle in pre-implantation mouse embryos. In the present study, we show that: (i) the cycling of channel activity is not prevented by inhibiting protein synthesis and hence does not involve cyclin-dependent kinase 1 (cdk1)-cyclin B; and (ii) the cycling of channel activity continues in anucleate zygote fragments with a time course similar to that observed in nucleate fragments. We further demonstrate that: (i) persistent activation of the K+ channel in one-cell embryos arrested in metaphase requires the maintenance of an active cdk1-cyclin B complex; and (ii) both DNA synthesis inhibition with aphidicolin and DNA damage produced by mitomycin C prevent the down-regulation of the channel at the start of S phase by a mechanism that requires tyrosine kinase activation. Thus, the 240 pS K+ channel in these cells is controlled by a previously unsuspected cytoplasmic clock that functions independently of the well-known clock controlling the chromosomal cell cycle, but can interact with it.
Day
M L
ML
Department of Physiology, University of Sydney, NSW 2006, Australia.
Johnson
M H
MH
Cook
D I
DI
D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D001683:Biological Clocks / Q000502:physiology; D001755:Blastocyst / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D019926:Cyclin B / Q000502:physiology; D015638:Cytochalasin D / Q000494:pharmacology; D003593:Cytoplasm / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011691:Puromycin / Q000494:pharmacology; D015053:Zygote / Q000502:physiology
D019926:Cyclin B; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D015638:Cytochalasin D; D016590:Aphidicolin; D011691:Puromycin; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D015739:Nocodazole; D002118:Calcium