A CYTOPLASMIC CELL-CYCLE CONTROLS THE ACTIVITY OF A K+ CHANNEL IN PREIMPLANTATION MOUSE EMBRYOS

We previously have reported that the activity of a 240 pS K+ channel v aries during the cell cycle in preimplantation mouse embryos. In the p resent 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 cha nnel activity continues in anucleate zygote fragments with a time cour se similar to that observed in nucleate fragments. We further demonstr ate that: (i) persistent activation of the K+ channel in one-cell embr yos arrested in metaphase requires the maintenance of an active cdk1-c yclin B complex; and (ii) both DNA synthesis inhibition with aphidicol in 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 ty rosine kinase activation. Thus, the 240 pS K+ channel in these cells i s controlled by a previously unsuspected cytoplasmic clock that functi ons independently of the well-known clock controlling the chromosomal cell cycle, but can interact with it.