DIFFERENTIAL MODULATION OF POTASSIUM CURRENTS BY CAMP AND ITS LONG-TERM AND SHORT-TERM EFFECTS - DUNCE AND RUTABAGA MUTANTS OF DROSOPHILA

The cAMP concentration in Drosophila is increased by mutations of the dunce (dnc) gene and decreased by mutations of die rutabaga (rut) gene. Such mutants provide a unique means for exploring the role of cAMP in functional and developmental regulation of membrane currents. Four distinct K+ currents have been identified in Drosophila larval muscle fibers, i.e. the voltage-activated transient I(A) and delayed I(K) and the Ca2+-activated fast I(CF) and slow I(CS). Results from our voltage-clamp studies indicated that both I(A) and I(K) were increased in dnc alleles. Normal muscle fibers treated with dibutyryl-cAMP showed a similar increase Of I(A), but no significant effect on I(K). In contrast to the dnc alleles, the rut mutations appeared to enhance I(CS) greatly while leaving the amplitude of other currents largely unchanged. In addition, the dibutyryl-cAMP-induced increase in I(A) was not observed in rut fibers. Caffeine and W7, which are known to interfere with several second messenger pathways, also modulted K+ currents in larval muscle fibers. The currents in dnc and rut fibers showed strikingly altered responses to caffeine and W7. The results demonstrate that the various K+ currents in Drosophila muscles are affected by altered cAMP cascades in the mutants. The fact that not all dnc and rut mutant defects can be mimicked or reversed by acute application of cAMP suggests that long-term modulation of K+ currents by cAMP may involve mechanisms distinct from the short-term effect of cAMP.