Alternative splicing in the pore-forming region of shaker potassium channels.
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, kappa-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.
Kim
M
M
Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, USA.
Baro
D J
DJ
Lanning
C C
CC
Doshi
M
M
Farnham
J
J
Moskowitz
H S
HS
Peck
J H
JH
Olivera
B M
BM
Harris-Warrick
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D020916:Conotoxins; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000494:pharmacology; D008121:Nephropidae / Q000235:genetics; D009498:Neurotoxins / Q000494:pharmacology; D009865:Oocytes; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation; D012326:RNA Splicing; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D051637:Shaker Superfamily of Potassium Channels; D013045:Species Specificity; D014162:Transfection; D014982:Xenopus laevis
D020916:Conotoxins; D018076:DNA, Complementary; D029721:Drosophila Proteins; D008978:Mollusk Venoms; D009498:Neurotoxins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels; C108818:kappa-conotoxin PVIIA