Unmasking of a novel potassium current in Drosophila by a mutation and drugs

Abstract

The delayed rectifier potassium current plays a critical role in cellular physiology. This current (I(K)) in Drosophila larvae is believed to be a single current. However, a likely null mutation in the Shab K+ channel gene (Shab3) reduces I(K) but does not eliminate it. This raises a question as to whether or not the entire I(K) passes through channels encoded by one gene. Similarly, an incomplete blockade of I(K) by high concentrations of quinidine, a selective I(K) blocker, raises a question as to whether I(K) consists of two components that are differentially sensitive to quinidine. We have addressed these questions by a combined use of genetics, pharmacology, and physiology. The current component removed by the Shab3 mutation differed from the remaining component in activation kinetics, inactivation kinetics, threshold of activation, and voltage dependence. The two components showed strong differences in sensitivity to quinidine. Physiological properties of the current component removed by the Shab3 mutation were similar to those of the quinidine-sensitive fraction of I(K). Complementary to this, properties of the current component remaining in the Shab3 mutant muscles were similar to those of the quinidine-resistant fraction of I(K). These observations strongly suggest that, in contrast to the current belief, I(K) consists of two components in Drosophila, which are genetically, pharmacologically, and physiologically distinct. These components are being called I(KS) and I(KF). I(KS) is carried via Shab-encoded channels. I(KF) defines a new voltage- activated K+ current in Drosophila.