Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5

RGK5 is a rat genomic DNA clone that encodes the n-type potassium channel found in T-lymphocytes and other cells. Current through this channel declines (inactivates) over a period of hundreds of milliseconds during a maintained depolarizing pulse, whether in lymphocytes or when expressed in Xenopus oocytes. Here we demonstrate that an amino acid residue near the outer pore of the channel, histidine⁴⁰¹, is involved in the inactivation process. Replacement of this residue by tyrosine, the amino acid found in the equivalent position of the homologous but non-inactivating channel RBK1, reduced inactivation of RGK5 over a 5 s depolarizing pulse from 84.3 ± 1.9% to 18.3 ± 1.1%. Conversely, replacement of this tyrosine in RBK1 (Tyr³⁷⁹) by histidine increased its inactivation from 21.6 ± 1.1% to 42.3 ± 1.5%. These results suggest a mechanism of channel inactivation distinct from that previously described for the A-type potassium channel.