A High Throughput Screening Technology-Overcoming Bottlenecks in Ion Channel Drug Targets

Ion Channels as therapeutic targets: Ion channels are transmembrane proteins that allow the formation of a concentration gradient between the extracellular and intracellular contents. Three major types of gated ion channels: (1) Ligand gated, (2) Mechanically gated and (3) Voltage gated channels are known to play pivotal roles in a variety of cellular processes within the human body and have been attributed to multiple diseases. Among the wide variety of ion channels, potassium channels are a diverse and ubiquitous family of ion channels present in both excitable and nonexcitable cells. Members of this channel family are involved in cellular signaling processes regulating neurotransmitter release, heart rate, neuronal excitability, smooth muscle contraction, insulin secretion, electrolyte transport and cell volume. Enhanced understanding of ion channel biology has correlated gene mutations in these channels with various diseases of the heart, kidney, pancreas, and central nervous system. Moreover, the combination of genomics, proteomics and biophysical approaches have remarkably progressed our knowledge on different aspects of these diseases. This knowledge helped in rationalizing how various mutations affect channel structure and function. The contribution of such mutations to the etiology of diseases and modulating the activity of ion channels has lead to the development of novel treatment strategies called channelopathies. Thus, regulating ion channel function is proving to be a successful approach in drug therapy.