A CHARACTERIZATION OF THE ACTIVATING STRUCTURAL REARRANGEMENTS IN VOLTAGE-DEPENDENT SHAKER K+ CHANNELS

In response to changes in membrane potential, voltage-dependent ion ch annel proteins undergo conformational rearrangements that lead to chan nel opening. These rearrangements move a net charge, measured as ''gat ing current,'' across the membrane. Here we characterize the effects o f the pharmacological blocker 4-aminopyridine on both the K+ and gatin g currents of wild-type and mutant Shaker K+ channels. Our results ind icate that the activation of these channels involves two distinct type s of structural rearrangement. In addition to independent Hodgkin and Huxley type rearrangements for each of the four subunits, which are re sponsible for most of the gating charge movement, Shaker channels inte rconvert between two quaternary conformations during activation. The t ransition between the two quaternary states moves about 10% of the tot al gating charge, and it is selectively blocked by 4-aminopyridine.