Figure 4: Split channels retain properties residing in both the voltage-sensing and permeation modules.

(a) Mutation of the voltage-sensor domain has similar effects in continuous and split channels. Neutralization of a positive charge in the S4 domain (R336Q) shifts the activation potential to hyperpolarized values regardless of the integrity of the S4–S5 linker (Open circles, wild type; closed circles, split channel; open diamonds, R336Q; closed diamonds, split R336Q; n=7; error bars, s.e.). (b) Blockade by astemizole, whose structural determinants lie in the C-terminal part of the protein, is conserved both in channels with interrupted S4–S5 (closed circles, n=6–7) or lacking completely the linker (squares, n=2–4), albeit with reduced affinity as compared with control (open circles, n=9–16). (c–e) A pore mutation precluding K⁺ permeation abolishes the activity also of split channels (c, wild-type split; d, G440S mutant split) (e) I/V relationship of wild-type and mutant split channels constructed with values obtained from 10 oocytes. Error bars represent s.e.