Alternative Splicing in the Pore-Forming Region ofshakerPotassium Channels

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 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.

Mouse heart Na+channels: primary structure and function of two isoforms and alternatively spliced variants

“…Alternative splicing has been reported to occur in the biosynthesis of innumerous proteins (1,24,45), including voltage-gated Na ϩ channels of the rat brain (21,32,39,42) and Drosophila (46). In case of the cardiac SCN5A isoform, alternatively spliced variants have not been reported so far.…”

ConusVenoms: A Rich Source of Novel Ion Channel-Targeted Peptides

“…Because the Shaker channel was cloned from Drosophila, this is not the natural target of -PVIIA; the latter has not been identified. Nevertheless, -PVIIA seems to be quite subtype selective; it was shown to differentiate between splice variants of the Shaker channel homolog from lobster (91). Injection of -PVIIA leads to excitatory symptoms in mice, but to date no cloned mammalian K channel (Ͼ20 tested so far) has been shown to be affected by this toxin.…”

Fine-tuning of Voltage Sensitivity of the Kv1.2 Potassium Channel by Interhelix Loop Dynamics

“…Even within the same subfamily, V 50 can vary widely between K v channels. In the K v 1 group, for example, published V 50 val-ues range from Ϫ46 mV in a lobster channel (20) to ϩ22 mV in a jellyfish channel (21). Human channels K v 1.1 and K v 1.2 share 80% sequence identity and yet differ in voltage sensitivity by 25 mV, with V 50 values of Ϫ30 mV and Ϫ5 mV, respectively (22).…”