Ion channels research in the post-genomic era

Ion channels are integral membrane proteins that catalyze the flux of ions across cell membranes, and play fundamental roles in a wide variety of functions throughout the body1. Thus, in the nervous system, various ion channels concert in regulating neuronal excitability, shaping action potentials, tuning neuronal firing patterns, and controlling transmitter release or synaptic integration. In the cardiovascular system, they control electrical excitability, impulse conduction and muscle contraction. In the kidney they regulate fluid secretion and electrolyte balance; and in the immune system, they drive exocytosis, stimulate mitochondrial metabolism, activate gene expression, and promote the activation, growth and proliferation of T cells. Moreover, ion channels also act as regulators in developmental processes and tissue patterning, and disruption of their function affects morphogenesis in flies, fishes, frogs and mammals. On the other hand, ion channels play essential roles in the pathophysiology of various diseases, and it is therefore not surprising that an ever-growing number of diseases are found to be caused by dysfunction of ion channels. Genetic defects in ion channels lead to severe neurological, cardiac, muscular or metabolic disorders, which are called 'channelopathies'1. As such, ion channels are recognized as important drug targets. In fact, a number of small molecule modulators of ion channels have been used clinically as anti-arrhythmic, anti-hypertensive, anti-epileptic or diuretic agents for decades