Satpal Singh

Associate professor

(716) 829-2453


Complete sequencing of human and other genomes has pointed to an extremely important role played by ion channel genes in many physiological processes. Genomic information also highlights the strong evolutionary conservation of molecular mechanisms across species. This makes genetic model systems, such as Drosophila, very powerful for understanding molecular mechanisms underlying most biological phenomena, including membrane excitability.

Using genetic protocols developed in our laboratory, we have identified more than 15 novel mutations that produce striking alterations in calcium and potassium currents in Drosophila. These mutations also affect other functions in flies, such as locomotor ability, heart rate, and/or sensitivity to the effects of pharmacological agents that act on ion channels. Cloning and molecular analysis of nine genes, and the gene products disrupted by these mutations, is underway in the laboratory. This analysis is yielding important information on modulation and regulation of ion channels, and their essential role in maintaining cellular physiology.

In addition to identifying and studying the above mutations, we are using existing mutations to analyze modulation of calcium channels via signal transduction pathways. By combining mutations with pharmacological agents, we have shown that the L-type calcium channels in Drosophila are modulated via the PLC - DAG - PKC pathway and a pathway involving PACAP, PAC1 receptors, adenylyl cyclase, cAMP, and PKA.

Regulation of Ca2+ and K+ channels plays an exceedingly important role in several neuromuscular and other functions, and these channels are targets of a number of pharmacological agents. To link our studies on Drosophila channels to those on channels in other systems, and to understand the mechanisms of ion channel regulation from a broader perspective, we are pursuing electrophysiological and pharmacological studies on the regulation of potassium and calcium channels in mammalian cells, and in cell lines, using patch-clamp recordings.