NEGATIVE CHARGES THAT SHARE IMPORTANT ELEMENTS OF FUNCTION IN CLONED CARDIAC K+ CHANNEL (KV1.5)

External Ht affected cloned cardiac Kf channel (Kv1.5) current expressed on Xenopus laevis oocytes in two different ways: the reduction in the maximal conductance (G(max)) and the shift of the activation curve in a depolarizing direction. The reduction in G(max) was affected by membrane potential in a concentration-dependent manner, suggesting that H+ entered and plugged the channel pore. The shift of the activation curve was explained by a ''fixed surface charge model''; the titration of surface negative charges by H+ was sensed by channel gating machinery, changing the voltage-dependence of channel activation. These data suggest that negatively charged amino acids exist on the wall inside the channel pore and on the external surface near the channel gating machinery, which share important elements of the function of Kv1.5 channel.