Research on inactivation of the hybrid K channel.

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We previously reported that the current observed in Kv1.4/Kv1.2 hybrid channel is very similar to that of the homotetrameric Kv1.4 channel ; which shows rapid inactivation during depolarizing pulses. It has been elucidated that in the hybrid channel the S4-S5 intracellular loop of non-inactivating subunit Kv1.2 could be part of the acceptor for the inactivation gates thetered from Kv1.4 subunit. This project was planned in order to investigate the relative contribution of the constitutive subunits to inactivation of the currents. The effects of a point mutation in the S4-S5 loop of Kv1.4 or Kv1.2 on inactivation of the hybrid channel were examined. Mutations in the S4-S5 loop of Kv1.4 and the corresponding amino acid of Kv1.2 had similar effects on inactivation time constant, suggesting that all of the S4-S5 loops derived from each constituent subunit equally contribute to inactivation as the acceptor for the inactivation gates.The role of the S5-S6 regions of Kv1.4 and Kv1.2 subunits in inactivation was also examined. The fusion genes encoding the hybrid channels were constructed, in which S5-S6 region of Kv1.4 or Kv1.2 was replaced with the corresponding region of Kv1.2 or Kv1.4, or the S5-S6 regions were interchanged between the two components. Characteristics of inactivation for all of these hybrid channels were similar. It was suggested from these results that the S5-S6 regions of all constituent subunits equally contribute to inactivation of the currents.