MODULATION OF TYPE-A K- EFFECTS OF THE OVEREXPRESSION OF FREQUENIN( CURRENT IN DROSOPHILA LARVAL MUSCLE BY INTERNAL CA2+ )

The calcium-dependent modulation of type A K+ current (I-A) has been i nvestigated using a two-electrode voltage clamp on larval muscle cells of Drosophila. It was found that the amplitude of I-A increases when [Ca2+](o) is changed from 0.2 mM to 2 mM. The increase in I-A amplitud e is not due to overlap with the Ca2+ -dependent fast K+ current, I-CF , since it is observed also in slo(1) mutants, which are deficient for this current. This effect is not due to Ca2+ -dependent shifts in the steady-state activation/inactivation kinetics. The phenomenon is prob ably due to elevations in internal calcium since it is abolished by Ca 2+ channel blockers and promoted by caffeine (5 mM) if added in the ab sence of external calcium. This calcium effect was dose-dependent sinc e it was not observed in the presence caffeine plus 2 mM calcium in th e bath nor for values of [Ca2+](o) above 4 mM. The Ca2+ -dependent mod ulation of I-A is absent in V7, a mutation that causes overexpression of frequenin, a recoverin-like Ca2+ -binding protein which stimulates guanylyl cyclase [31]. One possible explanation for the loss of I-A mo dulation in the V7 mutation is that the excess of frequenin alters int racellular cGMP-dependent metabolic pathways responsible for the inter nal calcium homeostasis.