Alternative splicing in the pore-forming region of shaker potassium channels

Marshall Kim, Deborah J. Baro, Cathy C. Lanning, Mehul Doshi, Jeremy Farnham, Howard S. Moskowitz, Jack H. Peck, Baldomero M. Olivera, Ronald M. Harris-Warrick

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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, 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, 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.

Original languageEnglish (US)
Pages (from-to)8213-8224
Number of pages12
JournalJournal of Neuroscience
Volume17
Issue number21
DOIs
StatePublished - 1997

Keywords

  • Alternative splicing
  • Conotoxin
  • Pore-forming region
  • Potassium channel
  • Shaker
  • Stomatogastric

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kim, M., Baro, D. J., Lanning, C. C., Doshi, M., Farnham, J., Moskowitz, H. S., Peck, J. H., Olivera, B. M., & Harris-Warrick, R. M. (1997). Alternative splicing in the pore-forming region of shaker potassium channels. Journal of Neuroscience, 17(21), 8213-8224. https://doi.org/10.1523/jneurosci.17-21-08213.1997