Electrostatics and the gating pore of Shaker potassium channels

Various experiments have suggested that the S4 segment in voltage-dependent Na+ and K+ channels is in contact with a solvent-accessible cavity. We exp lore the consequences of the existence of such a cavity through the electro static effects on the gating currents of ShakerK(+) channels under conditio ns of reduced ionic strength S. We observe that similar to 10-fold reductio ns of intracellular S produce reductions of the measured gating charge of s imilar to 10%. These effects continue at even lower values of S. The reduct ion of gating charge when S is reduced by 10-fold at the extracellular surf ace is much smaller (similar to2%). Shifts of the Q(V) curve because of a r educed S are small (<10 mV in size), which is consistent with very little f ixed surface charge. Continuum electrostatic calculations show that the S e ffects on gating charge can be explained by the alteration of the local pot ential in an intracellular conical cavity of 20-24-<Angstrom> depth and 12- Angstrom aperture, and a smaller extracellular cavity of 3-Angstrom depth a nd the same aperture. In this case, the attenuation of the membrane potenti al at low S leads to reduction of the apparent gating charge. We suggest th at this cavity is made by a bundle of transmembrane helices, and that the g ating charge movement occurs by translocation of charged residues across a thin septum of similar to3-7 Angstrom thickness.