K ⁺ Current Diversity Is Produced by an Extended Gene Family Conserved in Drosophila and Mouse

Abstract

The Drosophila Shaker gene on the X chromosome has three sister genes, Shal, Shab, and Shaw, which map to the second and third chromosomes. This extended gene family encodes voltage-gated potassium channels with widely varying kinetics (rate of macroscopic current activation and inactivation) and voltage sensitivity of steady-state inactivation. The differences in the currents of the various gene products are greater than the differences produced by alternative splicing of the Shaker gene. In Drosophila, the transient (A current) subtype of the potassium channel (Shaker and Shal) and the delayed-rectifier subtype (Shab and Shaw) are encoded by homologous genes, and there is more than one gene for each subtype of channel. Homologs of Shaker, Shal, Shab, and Shaw are present in mammals; each Drosophila potassium-channel gene may be represented as a multigene subfamily in mammals.

Maturation and myotonia influence the abundance of cation channels K DR , K IR and C IR differently: a patch-clamp study on mouse interosseus muscle fibres

“…However, the correlation between single-channel characteristics as determined by patch-clamp studies of cells expressing the ion channel under investigation naturally and the corresponding genes and their pattern of regulation is still rather incomplete for voltage-gated cation channels in general and K + channels in particular. The complex population of these channels as predicted from their genetic diversity [17,37], their variable physiological characteristics due to combination with accessory subunits and modulating mechanisms [3] and the scarcity of useful and specific blocking agents for these channels has hampered progress.…”

Functional diversity of potassium channel voltage-sensing domains

“…Also, their kinetics is highly variable, ranging from classical delayed rectifiers to rapidly inactivating A-type currents. 5,6 In spite of this diversity, we now know that the central mechanism of detection of voltage changes by Kv channels can be localized to the first 4 transmembrane segments, which assemble into a well-defined domain called the voltage sensing domain or VSD.…”

Alternative Splicing in the Pore-Forming Region ofshakerPotassium Channels

“…I A is not a uniform current, but it can be expressed with different properties (Wei et al, 1990). Different neurons can show markedly different types of I A , with varying maximal conductance, voltage dependence, and degree and rate of inactivation (Pfaffinger et al, 1991;Furakawa et al, 1992;Baro et al, 1996b).…”

“…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).…”