Multiple products of the drosophila Shaker gene may contribute to potassium channel diversity

Kamb, Alexander; Tseng-Crank, Julie; Tanouye, Mark A.

doi:10.1016/0896-6273(88)90192-4

Cited by 309 publications

(180 citation statements)

References 23 publications

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“…Substantially less homology was seen at the N terminus, where numerous alternative exons were found. In Drosophila, there was no significant homology between the alternatively spliced N termini (Kamb et al, 1988;Pongs et al, 1988;Schwarz et al, 1988), and in Panulirus the alternative exons did not resemble each Transmembrane-spanning domains S1-S6 and the pore-forming P region are labeled and shown in bold type. The sequences are 83% identical at the amino acid level.…”

Section: Comparing Panulirus and Drosophila Shakermentioning

confidence: 99%

“…In Drosophila, the transient K ϩ current is generated by the shak er and shal members of the Shak er family of potassium channels (Wu and Haugland, 1985;Papazian et al, 1987;Iverson et al, 1988;Kamb et al, 1988;Pongs et al, 1988;Timpe et al, 1988;Stocker et al, 1990;Wei et al, 1990). The Drosophila shaker subfamily transcript undergoes alternative splicing at the 5Ј and 3Ј ends of the coding region, with five alternative 5Ј ends and two alternative 3Ј ends (Kamb et al, 1988;Pongs et al, 1988;Schwarz et al, 1988).…”

mentioning

confidence: 99%

“…The Drosophila shaker subfamily transcript undergoes alternative splicing at the 5Ј and 3Ј ends of the coding region, with five alternative 5Ј ends and two alternative 3Ј ends (Kamb et al, 1988;Pongs et al, 1988;Schwarz et al, 1988). This alternative splicing generates up to 10 different proteins that form markedly different ion channel types, from rapidly inactivating A-type currents to slowly or noninactivating delayed rectifier-type currents.…”

mentioning

confidence: 99%

“…Functional channels are composed of tetramers of shaker proteins (Isacoff et al, 1990;MacKinnon, 1991), and heteromers can also be produced between the alternate splice forms of shaker, generating further diversity in channel types (Isacoff et al, 1990;McCormack et al, 1990;Ruppersberg et al, 1990;MacKinnon, 1991;Sheng et al, 1993;Wang et al, 1993). In Drosophila, all of these splice variants share a common conserved core region, which extends from before the first transmembrane region (S1) to the end of the pore-forming P region (Kamb et al, 1988;Pongs et al, 1988;Schwarz et al, 1988). Ion flux occurs through the P region, and site-directed mutagenesis of the amino acid sequence of this region has important functional consequences (MacKinnon et al, 1988;MacKinnon and Miller, 1989;MacKinnon and Yellen, 1990;Hartmann et al, 1991;Yellen et al, 1991;Yool and Schwarz, 1991;Heginbotham and MacKinnon, 1992).…”

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Alternative Splicing in the Pore-Forming Region ofshakerPotassium Channels

et al. 1997

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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 5Ј and 3Ј 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 ϩ currents or synaptic transmission between neurons.

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Section: Comparing Panulirus and Drosophila Shakermentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Alternative Splicing in the Pore-Forming Region ofshakerPotassium Channels

et al. 1997

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“…Currents carried by these channels have been separated into voltage-gated currents, such as the delayed rectifier, anomalous rectifier and transient (Ig) currents, and ligndgated currents, such as Ca2+-activated and ATPsensitive currents. Recent studies using recombinant DNA techniques indicate that in Drosophila melanogaster the Shaker gene complex encodes a family of K ÷ channels [1][2][3] with functional properties similar to the channels that mediate the transient, rapidly inactivating IA current observed in a variety of cell types in different species [4,5]. Using a low stringency hybridization protocol with a Drosophila Shaker cDNA probe a homologous cDNA, named RCK1, was isolated from a rat cerebral cortex library [6].…”

Section: Introductionmentioning

confidence: 99%