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Volume 17, Number 21, Issue of November 1, 1997 pp. 8213-8224
Copyright ©1997 Society for Neuroscience

Alternative Splicing in the Pore-Forming Region of shaker Potassium Channels

Received June 12, 1997; revised Aug. 15, 1997; accepted Aug. 21, 1997.

Marshall Kim¹, Deborah J. Baro¹, Cathy C. Lanning¹, Mehul Doshi¹, Jeremy Farnham¹, Howard S. Moskowitz¹, Jack H. Peck², Baldomero M. Olivera³, and Ronald M. Harris-Warrick¹

¹ Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, ² Department of Psychology, Ithaca College, Ithaca, New York 14850, and ³ Department of Biology, University of Utah, Salt Lake City, Utah 84112

We have cloned cDNAs for the shaker potassium channel gene from the spiny lobster Panulirus interruptus. As previously found in Drosophila, there is alternative splicing at the 5 and 3 ends of the coding region. However, in Panulirus 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, -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, and Panulirus shal were not blocked. When it was tested in the Panulirus stomatogastric ganglion, the toxin produced no effects on transient K⁺ currents or synaptic transmission between neurons.

Key words: potassium channel; shaker; stomatogastric; pore-forming region; alternative splicing; conotoxin

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