Fast pseudo-periodic oscillation in the rat brain voltage-gated sodium channel α subunit

Abstract

In the work reported here, we have investigated the changes in the activation and fast inactivation properties of the rat brain voltage-gated sodium channel (rNa_ν 1.2a) α subunit, expressed heterologously in the Chinese Hamster Ovary (CHO) cells, by short depolarizing prepulses (10 - 1000 ms). The time constant of recovery from fast inactivation (τ_fast) and steady-state parameters for activation and inactivation varied in a pseudo-oscillatory fashion with the duration and amplitude of a sustained prepulse. A consistent oscillation was observed in most of the steady-state and non-inactivating current parameters with a time period close to 225 ms, although a faster oscillation of time period 125 ms was observed in the τ_fast. The studies on the non-inactivating current and steady-state activation indicate that the phase of oscillation varies from cell to cell. Co-expression of the β1 subunit with the α subunit channel suppressed the oscillation in the charge movement per single channel and free energy of steady-state inactivation, although the oscillation in the half steady-state inactivation potential remained unaltered. Incidentally, the frequencies of oscillation in the sodium channel parameters (4-8 Hz) correspond to the theta component of network oscillation. This fast pseudo-oscillatory mechanism, together with the slow pseudo-oscillatory mechanism found in these channels earlier, may contribute to the oscillations in the firing properties observed in various neuronal subtypes and many pathological conditions.