Update on tandem pore (2P) domain K+ channels

The volatile anesthetics are widely used in clinical practice today to produce a state of general anesthesia. But despite more than 150 years of use and substantial scientific investigation, the mechanism by which they produce central nervous system depression remains elusive. Complete understanding of the cellular and molecular basis of the anesthetized state produced by volatile anesthetics most likely involves modulation of the activity of ion channel proteins; these macromolecules provide the most likely molecular targets for these agents. Many studies suggest the involvement of GABAergic and glutamatergic receptor systems in mediating the action of volatile anesthetics. Another ionic current found ubiquitously in neuronal tissues, background potassium currents (also known as resting or leak K+ currents), have recently emerged as plausible targets for volatile anesthetics. A unique structural class of K+ channels with two pore-forming sequences in tandem (2P K+ channels) contributes significantly to background K+ currents. The complete identification of all the 2P K+ channel family members has likely been accomplished. Within intact neuronal systems, background K+ channels are responsible for essential inhibition; these actions are enhanced by volatile anesthetics. Thus, members of this family have emerged as strong candidates for the molecular site of volatile anesthetic action.