Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA-sensitive, type-A K+ channel

Transient voltage-dependent potassium (K+) currents, also known as A currents, have been of great interest to neurophysiologists due to their special roles in neuronal excitability. Several cDNAs encoding transcripts expressing A currents have been characterized. Recently, a cDNA (KShIIIC or Raw3) was isolated which expresses an unusual A current that is highly sensitive to TEA, and activates at potentials more positive than -20 mV. Channels containing this protein may have specialized roles in modulating the electrical behaviour of neurons. Here we report the isolation and characterization of two rat cDNAs corresponding to two alternatively spliced transcripts (KShIIID.1 and KShIIID.2) from another gene (KShIIID) of the same subfamily as KShIIIC, the ShIII or Shaw-related gene subfamily. KShIIID.1 also expresses an unusual high-voltage-activating, TEA-sensitive A-type channel. There are, however, significant differences between KShIIIC and KShIIID channels which may have interesting functional consequences. The two most important differences are: (i) KShIIID channels conduct in the steady-state over a much broader window of potentials than KShIIIC; this reflects differences between the kinetic schemes of the two channels; and (ii) KShIIID inactivates with significantly slower kinetics than KShIIIC. The identification of KShIIID transcripts contributes to our knowledge of the molecular components that may determine the functional diversity of A currents and provides exciting opportunities to increase our understanding of the structure and function of K+ channels.