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

Auxiliary Hyperkinetic beta subunit of K+ channels: regulation of firing properties and K+ currents in Drosophila neurons. J. Neurophysiol. 81: 2472-2484, 1999. Molecular analysis and heterologous expression have shown that K+ channel beta subunits regulate the properties of the pore-forming or subunits, although how they influence neuronal Kf currents and excitability remains to be explored. We studied cultured Drosophila "giant'' neurons derived from mutants of the Hyperkinetic (Hk) gene, which codes for a K+ channel beta subunit. Whole cell patch-clamp recording revealed broadened action potentials and, more strikingly, persistent rhythmic spontaneous activities in a portion of mutant neurons. Voltage-clamp analysis demonstrated extensive alterations in the kinetics and voltage dependence of K+ current activation and inactivation, especially at subthreshold membrane potentials, suggesting a role in regulating the quiescent state of neurons that are capable of tonic tiring. Altered sensitivity of Hk currents to classical K+ channel blockers (4-aminopyridine, alpha-dendrotoxin, and TEA) indicated that Hk mutations modify interactions between voltage-activated K+ channels and these pharmacological probes, apparently by changing both the intra- and extracellular regions of the channel pore. Correlation of voltage- and current-clamp data from the same cells indicated that Hk mutations affect not only the persistently active neurons, but also other neuronal categories. Shaker (Sh) mutations, which alter K+ channel or subunits, increased neuronal excitability 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 conferred by intact Sh alpha subunits in a distinct neuronal subpopulation. Our results suggest that alterations in beta subunit regulation, rather than elimination or addition of alpha subunits, may cause striking modifications in the excitability state of neurons, which may be important for complex neuronal function and plasticity.