Alternative Splicing in the Pore-Forming Region ofshakerPotassium Channels

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Abstract
We have cloned cDNAs for theshakerpotassium channel gene from the spiny lobsterPanulirus interruptus. As previously found inDrosophila, there is alternative splicing at the 5′ and 3′ ends of the coding region. However, inPanulirus shaker, alternative splicing also occurs within the pore-forming region of the protein. Three different splice variants were found within the P region, two of which bestow unique electrophysiological characteristics to channel function. Pore I and pore II variants differ in voltage dependence for activation, kinetics of inactivation, current rectification, and drug resistance. The pore 0 variant lacks a P region exon and does not produce a functional channel. This is the first example of alternative splicing within the pore-forming region of a voltage-dependent ion channel. We used a recently identified potassium channel blocker, κ-conotoxin PVIIA, to study the physiological role of the two pore forms. The toxin selectively blocked one pore form, whereas the other form, heteromers between the two pore forms, andPanulirus shalwere not blocked. When it was tested in thePanulirusstomatogastric ganglion, the toxin produced no effects on transient K+currents or synaptic transmission between neurons.