ALTERNATIVE SPLICING IN THE PORE-FORMING REGION OF SHAKER POTASSIUM CHANNELS

We have cloned cDNAs for the shaker potassium channel gene from the sp iny lobster Panulirus interruptus. As previously found in Drosophila, there is alternative splicing at the 5' and 3' ends of the coding regi on. However, in Panulirus shaker, alternative splicing also occurs wit hin the pore-forming region of the protein. Three different splice var iants were found within the P region, two of which bestow unique elect rophysiological characteristics to channel function. Pore I and pore I I variants differ in voltage dependence for activation, kinetics of in activation, current rectification, and drug resistance. The pore 0 var iant lacks a P region exon and does not produce a functional channel. This is the first example of alternative splicing within the pore-form ing region of a voltage-dependent ion channel. We used a recently iden tified potassium channel blocker, kappa-conotoxin PVIIA, to study the physiological role of the two pore forms. The toxin selectively blocke d one pore form, whereas the other form, heteromers between the two po re forms, and Panulirus shal were not blocked. When it was tested in t he Panulirus stomatogastric ganglion, the toxin produced no effects on transient K+ currents or synaptic transmission between neurons.