KN-62, AN INHIBITOR OF CA2+/CALMODULIN KINASE-II, ATTENUATES CIRCADIAN RESPONSES TO LIGHT

EXPRESSION of immediate early genes and phosphorylation of the transcription factor CREB are induced in the suprachiasmatic nucleus after light pulses that cause phase shifts of circadian rhythms. To test for a direct role of this signalling pathway in mediating circadian responses to light in hamsters, we used KN-62 to inhibit the activity of CaM kinase II (known to phosphorylate CREB) prior to giving light pulses at times that would normally induce phase shifts. Central administration of KN-62 significantly inhibited phase delays and advances induced by bright pulses of light. The data support a model for photic responses of the circadian clock in the SCN that includes the phosphorylation of CREB by activation of CaM kinase II.