Focus Issue: Ion Channels: Opening the Gateless Gate "When one passes through this gateless gate, he walks freely between heaven and earth." The Wu-men kuan (The Mumonkan, The Gateless Gate) ()

Channels, receptors, and carrier proteins in the plasma membrane comprise the initial springboard for communication between the external environment and the cell interior. Ion channels, which exploit the differences in electrolyte composition between the internal and external cellular milieu to transmit electrical and chemical signals, provide the most rapid and perhaps the most direct means of information transfer across the cell membrane. A host of channels has evolved that show selective permeability to different ionic species and that respond to various input modalities. Perhaps the most familiar of these are the sodium and potassium channels that underlie the propagated action potential of many excitable cells. These channels are voltage-gated: They change conformation and become permeable to ions in response to changes in the potential difference across the cell membrane. The ensuing ionic fluxes lead to the changes in membrane potential that allow the action potential to regenerate itself and propagate down an axon or through a muscle fiber. Some excitable cells exhibit persistent depolarizing currents and are spontaneously active. The firing of such cells can be modulated--or the firing of quiescent cells stimulated--by input from mechanically gated channels that open in response to deformation of the cell membrane or from ligand-gated channels, such as those that open in response to the binding of neurotransmitter. Some channels are indirectly gated--or otherwise modulated--in response to the activation of various intracellular second messenger pathways.