Simple fluctuation of Ca2+ elicits the complex circadian dynamics of cyclic AMP and cyclic GMP in Paramecium

The circadian dynamics of cyclic adenosine 3',5'-monophosphate (cAMP) and c yclic guanosine 3',5'-monophosphate (cGMP) were simulated in Paramecium mul timicronucleatum. The mathematical functions determined closely mimic the C a2+ dependence of adenylate cyclase (AC) and guanylate cyclase (GC) activit ies as documented in P. tetraurelia. Patterns of cAMP concentration ([cAMP] ), cGMP concentration ([cGMP]), and the ratio [cGMP]/[cAMP] were calculated with respect to Ca2+ concentrations ([Ca2+]) fluctuating sinusoidally with a period of 24 hours at three different levels: low medium, and high. The functions displayed varying patterns of [cAMP] characteristic for [Ca2+] fl uctuating at each level, while patterns of [cGMP] and [cGMP]/[cAMP] almost paralleled [Ca2+] fluctuations. Similar patterns were observed for actual [ cAMP] and [cGMP] measured during the light/dark cycle in P. multimicronucle atum, grown in axenic media additionally containing [Ca2+] at 25 (low), 100 (medium), or 400 (high) mu M, respectively. The coincidence between simula ted and measured fluctuations of [cAMP] and [cGMP] suggests that the circad ian fluctuations of intracellular [Ca2+] primarily stimulate activities of AC and GC via their different degrees of Ca2+ dependence, which are ultimat ely responsible for the circadian spatiotemporal organization of various ph ysiological functions in Paramecium.