MOLECULAR-BASIS FOR DIFFERENT PORE PROPERTIES OF POTASSIUM CHANNELS FROM THE RAT-BRAIN KV1 GENE FAMILY

Members of the rat brain Kv1 family of cloned potassium channels are s tructurally highly homologous, but have diverse conductance and pharma cological characteristics. Here we present data on the effects of muta ting residues K533 in the P-region and H471 in the S4-S5 linker of Kv1 .4 to their equivalent residues in Kv1.1 and Kv1.6 on single-channel c onductance and sensitivity to external tetraethylammonium cations (TEA (+)) and internal Mg2+. Exchange of residue K533 for its equivalent re sidue (Y) in Kv1.1 and Kv1.6 increased the single-channel conductance at both negative and positive potentials. This mutation is known to re duce the IC50 for external TEA(+) from > 100 mM to 0.6 mM, almost iden tical to that for Kv1.1 (0.53 mM). We have now found that the addition al exchange of residue H471 for the equivalent residue (K) in Kv1.6 in creased the IC50 for external TEA(+) from 0.6 mM (Kv1.4K533Y) to 2.39 mM; this is very close to that for wild-type Kv1.6 channels (2.84 mM). The mutation H471K alone was ineffective. We thus provide evidence th at the S4-S5 linker does contribute to the channel's inner-port region . Data on the block of Kv1 channels by internal Mg2+ indicate that whi le the binding site is probably situated within the deep-pore region, its exact location may be channel specific.