Modulation of jellyfish potassium channels by external potassium ions

The amplitude of an A-like potassium current (I-Kfast) in identified cultur ed motor neurons isolated from the jellyfish Polyorchis penicillatus was fo und to be strongly modulated by extracellular potassium ([K+](out)). When e xpressed in Xenopus oocytes, two jellyfish Shaker-like genes, jShak1 and jS hak2, coding for potassium channels, exhibited similar modulation by [K+](o ut) over a range of concentrations from 0 to 100 mM. jShak2-encoded channel s also showed a decreased rate of inactivation and an increased rate of rec overy from inactivation at high [K+](out). Using site-directed mutagenesis we show that inactivation of jShak2 can be ascribed to an unusual combinati on of a weak "implicit" N-type inactivation mechanism and a strong, fast, p otassium-sensitive C-type mechanism. Interaction between the two forms of i nactivation is responsible for the potassium dependence of cumulative inact ivation. Inactivation of jShak1 was determined primarily by a strong "ball and chain" mechanism similar to fruit fly Shaker channels. Experiments usin g fast perfusion of outside-out patches with jShak2 channels were used to e stablish that the effects of [K+](out) on the peak current amplitude and in activation were due to processes occurring at either different sites locate d at the external channel mouth with different retention times for potassiu m ions, or at the same site(s) where retention time is determined by state- dependent conformations of the channel protein. The possible physiological implications of potassium sensitivity of high-threshold potassium A-like cu rrents is discussed.