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 explore the consequences of the existence of such a cavity through the electrostatic effects on the gating currents of ShakerK(+) channels under conditions of reduced ionic strength S. We observe that similar to 10-fold reductions of intracellular S produce reductions of the measured gating charge of similar to 10%. These effects continue at even lower values of S. The reduction of gating charge when S is reduced by 10-fold at the extracellular surface is much smaller (similar to2%). Shifts of the Q(V) curve because of a reduced S are small (<10 mV in size), which is consistent with very little fixed surface charge. Continuum electrostatic calculations show that the S effects on gating charge can be explained by the alteration of the local potential in an intracellular conical cavity of 20-24- depth and 12-Angstrom aperture, and a smaller extracellular cavity of 3-Angstrom depth and the same aperture. In this case, the attenuation of the membrane potential at low S leads to reduction of the apparent gating charge. We suggest that this cavity is made by a bundle of transmembrane helices, and that the gating charge movement occurs by translocation of charged residues across a thin septum of similar to3-7 Angstrom thickness.