Auxiliary Hyperkinetic beta subunit of K+ channels: Regulation of firing properties and K+ currents in Drosophila neurons

Auxiliary Hyperkinetic beta subunit of K+ channels: regulation of firing pr operties and K+ currents in Drosophila neurons. J. Neurophysiol. 81: 2472-2 484, 1999. Molecular analysis and heterologous expression have shown that K + channel beta subunits regulate the properties of the pore-forming or subu nits, although how they influence neuronal Kf currents and excitability rem ains to be explored. We studied cultured Drosophila "giant'' neurons derive d from mutants of the Hyperkinetic (Hk) gene, which codes for a K+ channel beta subunit. Whole cell patch-clamp recording revealed broadened action po tentials and, more strikingly, persistent rhythmic spontaneous activities i n a portion of mutant neurons. Voltage-clamp analysis demonstrated extensiv e alterations in the kinetics and voltage dependence of K+ current activati on and inactivation, especially at subthreshold membrane potentials, sugges ting a role in regulating the quiescent state of neurons that are capable o f tonic tiring. Altered sensitivity of Hk currents to classical K+ channel blockers (4-aminopyridine, alpha-dendrotoxin, and TEA) indicated that Hk mu tations modify interactions between voltage-activated K+ channels and these pharmacological probes, apparently by changing both the intra- and extrace llular regions of the channel pore. Correlation of voltage- and current-cla mp data from the same cells indicated that Hk mutations affect not only the persistently active neurons, but also other neuronal categories. Shaker (S h) mutations, which alter K+ channel or subunits, increased neuronal excita bility but did nor cause the robust spontaneous activity characteristic of some Hk neurons. Significantly, Hk Sh double mutants were indistinguishable from Sh single mutants, implying that the rhythmic Hk firing pattern is co nferred by intact Sh alpha subunits in a distinct neuronal subpopulation. O ur results suggest that alterations in beta subunit regulation, rather than elimination or addition of alpha subunits, may cause striking modification s in the excitability state of neurons, which may be important for complex neuronal function and plasticity.