Characterization of a Neuronal Delayed Rectifier K Current Permeant to Cs and Blocked by Verapamil

Abstract.

We have used the patch-clamp method in the whole-cell configuration to characterize the delayed rectifier K current (I _DRK) in embryonic chick dorsal root ganglion (DRG) neurons. The I _DRK is activated by depolarizing pulses positive to −40 mV, and its V _½ is near −20 mV. The slope factor of 10.4 mV for an e-fold change in conductance indicates an equivalent gating charge of 2.4e. Inactivation during sustained depolarizing pulses displays two distinct time constants of 200–300 msec and 6–9 sec, respectively. Outward current through the delayed rectifier K (DRK) channels could also be carried by internal Cs, which however exerts mild block when in mixtures with K, as evidenced by the anomalous mole fraction effect. The relative permeability of Cs vs. K, P_Cs/P_K, as calculated from reversal potential measurements, is 0.25. Rb likewise permeates the DRK channel (P_Rb/P_K= 0.67). The I _DRK was effectively suppressed by external application of the Ca channel blocker Verapamil, with apparent dissociation constant of ca. 4 μm. The time course of Verapamil block, its good description by equations derived from open-channel block kinetic scheme, and the frequency-dependent effect of the blocker indicate that Verapamil can bind to the channel only when it is in the open state.