Once ingested by mosquitoes, malaria parasites undergo complex cellular changes. 
These include zygote formation, transformation of zygote to ookinete, and 
differentiation from ookinete to oocyst. Within the oocyst, the parasite 
multiplies into numerous sporozoites. Modulators of intracellular calcium 
homeostasis, MAPTAM, and TMB-8 blocked ookinete development as did the 
calmodulin (CaM) antagonists W-7 and calmidazolium. Ca(2+)/CaM-dependent protein 
kinase inhibitor KN-93 also blocked zygote elongation, while its ineffective 
analog KN-92 did not have such effect. In vitro both zygote and ookinete 
extracts efficiently phosphorylated autocamtide-2, a classic CaM kinase 
substrate, which could be blocked by calmodulin antagonists W-7 and 
calmidazolium and CaM kinase inhibitor KN-93. These results demonstrated the 
presence of calmodulin-dependent CaM kinase activity in the parasite. 
KN-93-treated parasites, however, expressed the ookinete-specific enzyme 
chitinase and the ookinete surface antigen Pgs28 normally, suggesting that the 
morphologically untransformed parasites are biochemically mature ookinetes. In 
mosquitoes, KN-93-treated parasites did not develop as oocysts, while 
KN-92-treated parasites produced similar numbers of oocysts as controls. These 
data suggested that in Plasmodium gallinaceum morphological development of 
zygote to ookinete, but not its biochemical maturation, relies on 
Ca(2+)/CaM-dependent protein kinase activity and demonstrated that the 
morphological differentiation is essential for the further development of the 
parasite in infected blood-fed mosquitoes.