A novel non-neuronal hSK3 isoform with a dominant-negative effect on hSK3 currents.

We have identified a hSK3-transcript, hSK3_ex1c, which is generated by alternative splicing. Isoform hSK3_ex1c lacks the cytosolic N-terminus and the first transmembrane helix and is exclusively expressed in non-neuronal tissues. hSK3 transfected tsA cells showed a Ca2+-activated K+ current in patch-clamp experiments, whereas hSK3_ex1c transfected cells and cells co-transfected with both isoforms did not. We fused both isoforms to fluorescence proteins and observed hSK3 localization predominantly in the plasma membrane. The co-expression of hSK3 + hSK3_ex1c resulted in their cytoplasmic co-localization. Thus, hSK3_ex1c has a dominant-negative effect on hSK3 by preventing its transport into the plasma membrane.