Electrophysiological characterization of sodium‐activated potassium channels in NG108‐15 and NSC‐34 motor neuron‐like cells

Abstract

The electrical properties of Na(+) -activated K(+) current (I(K(Na)) ) and its contribution to spike firing has not been characterized in motor neurons. We evaluated how activation of voltage-gated K(+) current (I(K) ) at the cellular level could be coupled to Na(+) influx through voltage-gated Na(+) current (I(N) (a) ) in two motor neuron-like cells (NG108-15 and NSC-34 cells). Increasing stimulation frequency altered the amplitudes of both I(Na) and I(K) simultaneously. With changes in stimulation frequency, the kinetics of both I(Na) inactivation and I(K) activation were well correlated at the same cell. Addition of tetrodotoxin or ranolazine reduced the amplitudes of both I(Na) and I(K) simultaneously. Tefluthrin (Tef) increased the amplitudes of both I(Na) and I(K) throughout the voltages ranging from -30 to+10mV. In cell-attached recordings, single-channel conductance from a linear current-voltage relation was 94±3pS (n=7). Tef (10μm) enhanced channel activity with no change in single-channel conductance. Tef increased spike firing accompanied by enhanced facilitation of spike-frequency adaptation. Riluzole (10μm) reversed Tef-stimulated activity of K(Na) channels. In motor neuron-like NSC-34 cells, increasing stimulation frequency altered the kinetics of both I(Na) and I(K) . Modelling studies of motor neurons were simulated to demonstrate that the magnitude of I(K(Na)) modulates AP firing. There is a direct association of Na(+) and K(Na) channels which can provide the rapid activation of K(Na) channels required to regulate AP firing occurring in motor neurons.