Gene dosage and complementation analysis of the Shaker locus in Drosophila.

Mutations of the Shaker (Sh) locus alter or eliminate a transient, voltage-sensitive potassium current, the "A" current, in flight muscle of Drosophila. We show that the amplitude of the A current is reduced when the dosage of Sh+ is lower than normal, but that A current amplitude does not increase as extra copies of Sh+ are added. We have also examined 14 Shaker mutants by voltage clamp and by intracellular recording at the larval neuromuscular junction. In 10 of these mutants there is no detectable fast component of the transient outward current. In each of these 10, however, a small, slowly inactivating, outward current is present. The 10 mutations null for the fast component of the transient, outward current are all partially dominant, giving 50-80% of the normal A current in Shnull/Sh+ heterozygotes. Because as little as 5% of the normal A current can be detected, complementation tests are feasible. The 10 null mutations are members of a single complementation group. The remaining 4 mutations have reduced A currents in pupal flight muscle. In all cases, crosses between these leaky mutants and null mutants give progeny with less A current than found in the leaky parental lines, as would be expected if the leaky and null mutations are in the same complementation group. For 1 of the mutations, ShrKO120, the mutant phenotype is much more severe in nerve than in muscle. That part of the Shaker locus required for the production of the A channel lies between the B55 and the V7 translocation breakpoints, in region 16F of the X chromosome.