Variable ratio of permeability to gating charge of rBIIA sodium channels and sodium influx in Xenopus oocytes

Whole-cell gating current recording from rat brain IIA sodium channels in X enopus oocytes was achieved using a high-expression system and a newly deve loped high-speed two-electrode voltage-clamp. The resulting ionic currents were increased by an order of magnitude. Surprisingly, the measured corresp onding gating currents were similar to5-10 times larger than expected from ionic permeability. This prompted us to minimize uncertainties about clamp asymmetries and to quantify the ratio of sodium permeability to gating char ge, which initially would be expected to be constant for a homogeneous chan nel population. The systematic study, however, showed a 10- to 20-fold vari ation of this ratio in different experiments, and even in the same cell dur ing an experiment. The ratio of P-Na/Q was found to correlate with substant ial changes observed for the sodium reversal potential. The data suggest th at a cytoplasmic sodium load in Xenopus oocytes or the energy consumption r equired to regulate the increase in cytoplasmic sodium represents a conditi on where most of the expressed sodium channels keep their pore closed due t o yet unknown mechanisms. In contrast, the movements of the voltage sensors remain undisturbed, producing gating current with normal properties.