Some residues in the inner vestibule of the hKv1.3 channel provide important binding sites for small molecule inhibitors and some are involved in its characteristic C-type inactivation. In order to obtain information about the role of single amino acids in this area of the hKv1.3 channel we generated a cysteine mutation in the pore region at position 388 (Shaker position 438). The measurements were performed with the whole-cell recording mode of the patchclamp technique using a ramp protocol from -200 mV to +80 mV. In potassium containing extracellular solution and KF intracellularly we observed a similar current to that of the reduced inactivating hKv1.3 H399T mutant. In extracellular solutions containing only Na+ or NH4+ we found that the V388C mutant channel showed a different current behaviour compared to the hKv1.3 H399T mutant. There was no expected potassium outward current between -40 mV and +80 mV and at potentials more negative than -120 mV we observed a current which looked like an inward current of Na+ and NH4+ through the channel. The hKv1.3 V388C mutant seems to promote influx of Na+ and NH4+ and, in addition, leads to a change in the gating properties of the channel.

Supported by grants from the 4SC AG (Martinsried), the Wilhelm- Sander-Stiftung (2004.046.1) and the Land Baden-Württemberg (1423/74).