Single Channel Seeks Permeant Ion for Brief but Intimate Relationship

Ion channels don't like having their permeant ions taken away. Particularly when they are in the mood to let ions through, this sort of deprivation makes them feel downright unstable. Like jilted lovers, they shut the door and become listless, inactive(-ated), and sometimes even immobilized. Channel physiologists have long tried to ignore this dejected behavior on the part of the channels , even though for many years it has been clear that channels often refuse to gate normally in unfriendly ionic conditions. The best known such effect is the slowed closing of channels in the presence of high concentrations of certain permeant ions, often called the " foot in the door " effect (Yeh and Armstrong, 1978). This type of effect was first noticed for synaptic channels (Ascher et al., 1978; Marchais and Marty, 1979) and has been studied in detail for a variety of K ϩ channels (Stanfield et al. Three recent papers in this journal highlight the different possible manifestations of such ion effects on gating and emphasize their importance for a good bio-physical understanding of the channel mechanisms. Cloned voltage-activated Na ϩ channels show two distinct changes in gating when extracellular Na ϩ ions are replaced by impermeant ions (Townsend et al., 1997; Townsend and Horn, 1997). The first change is that their open probability is reduced, particularly for very large depolarizations. This decrease is not seen with normal concentrations of extracellular Na ϩ and is likely to result from a voltage-dependent depletion of ions from the pore. Only the highly permeant ions Na ϩ and Li ϩ can prevent this effect, which does not depend on the normal fast inactivation mechanism. In fact, it is more prominent in a mutant with reduced fast inactiva-tion. Townsend et al. (1997) show that the ion-sensitive steps are very rapid, and they argue that the most likely explanation of the effect is that, in the absence of extra-cellular permeant ions, there is a rapid inactivation that competes with the opening process. The second effect of reduced Na ϩ concentration is to enhance Na ϩ channel slow inactivation (Townsend and Horn, 1997). In low [Na ϩ ], the onset of inactivation is faster and recovery is slower. In contrast with the rapid ion effects on open probability, all of the alkali cations tested can oppose slow inactivation, even the weakly permeant K ϩ and Cs ϩ ions. Both of these effects …