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• Effects of external cesium and rubidium on outward potassium...

  Effects of external cesium and rubidium on outward potassium currents in squid axons Biophysical Journal, Volume 42, Issue 1, 1 April 1983, Pages 43-53 J.R. Clay and M.F. Shlesinger Abstract We have studied the effects of external cesium and rubidium on potassium conductance of voltage clamped squid axons over a broad range of concentrations of these ions relative to the external potassium concentration. Our primary novel finding concerning cesium is that relatively large concentrations of this ion are able to block a small, but statistically significant fraction of outward potassium current for potentials less than approximately 50 mV positive to reversal potential. This effect is relieved at more positive potentials. We have also found that external rubidium blocks outward current with a qualitatively similar voltage dependence. This effect is more readily apparent than the cesium blockade, occurring even for concentrations less than that of external potassium. Rubidium also has a blocking effect on inward current, which is relieved for potentials more than 20–40 mV negative to reversal, thereby allowing both potassium and rubidium ions to cross the membrane. We have described these results with a single-file diffusion model of ion permeation through potassium channels. The model analysis suggests that both rubidium and cesium ions exert their blocking effects at the innermost site of a two-site channel, and that rubidium competes with potassium ions for entry into the channel more effectively than does cesium under comparable conditions. Abstract | PDF (1350 kb)

• Gating and Flickery Block Differentially Affected by Rubidiu...

  Gating and Flickery Block Differentially Affected by Rubidium in Homomeric KCNQ1 and Heteromeric KCNQ1/KCNE1 Potassium Channels Biophysical Journal, Volume 78, Issue 1, 1 January 2000, Pages 211-226 Michael Pusch, Lara Bertorello and Franco Conti Abstract The voltage-gated potassium channel KCNQ1 associates with the small KCNE1 subunit to form the cardiac IKs delayed rectifier potassium current and mutations in both genes can lead to the long QT syndrome. KCNQ1 can form functional homotetrameric channels, however with drastically different biophysical properties compared to heteromeric KCNQ1/KCNE1 channels. We analyzed gating and conductance of these channels expressed in oocytes using the two-electrode voltage-clamp and the patch-clamp technique and high extracellular potassium (K) and rubidium (Rb) solutions. Inward tail currents of homomeric KCNQ1 channels are increased about threefold upon substitution of 100mM potassium with 100mM rubidium despite a smaller rubidium permeability, suggesting an effect of rubidium on gating. However, the kinetics of tail currents and the steady-state activation curve are only slightly changed in rubidium. Single-channel amplitude at negative voltages was estimated by nonstationary noise analysis, and it was found that rubidium has only a small effect on homomeric channels (1.2-fold increase) when measured at a 5-kHz bandwidth. The apparent single-channel conductance was decreased after filtering the data at lower cutoff frequencies indicative of a relatively fast “flickery/block” process. The relative conductance in rubidium compared to potassium increased at lower cutoff frequencies (about twofold at 10Hz), suggesting that the main effect of rubidium is to decrease the probability of channel blockage leading to an increase of inward currents without large changes in gating properties. Macroscopic inward tail currents of heteromeric KCNQ1/KCNE1 channels in rubidium are reduced by about twofold and show a pronounced sigmoidal time course that develops with a delay similar to the inactivation process of homomeric KCNQ1, and is indicative of the presence of several open states. The single channel amplitude of heteromers is about twofold smaller in rubidium than in potassium at a bandwidth of 5kHz. Filtering at lower cutoff frequencies reduces the apparent single-channel conductance, the ratio of the conductance in rubidium versus potassium is, however, independent of the cutoff frequency. Our results suggest the presence of a relatively rapid process (flicker) that can occur almost independently of the gating state. Occupancy by rubidium at negative voltages favors the flicker-open state and slows the flickering rate in homomeric channels, whereas rubidium does not affect the flickering in heteromeric channels. The effects of KCNE1 on the conduction properties are consistent with an interaction of KCNE1 in the outer vestibule of the channel. Abstract | Full Text | PDF (280 kb)

• Biophysics of Ion Permeation

  Biophysics of Ion Permeation Biophysical Journal, Volume 94, Issue , 1 February 2008, Pages 739-748 Full Text | PDF (162 kb)

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Abstract

The influence of a gramicidin-like channel former on ion free energy barriers is studied using Monte Carlo simulation. The model explicitly describes the ion, the water dipoles, and the peptide carbonyls; the remaining degrees of freedom, bulk electrolyte, non-polar lipid and peptide regions, and electronic (high frequency) permittivity, are treated in continuum terms. Contributions of the channel waters and peptide COs are studied both separately and collectively. We found that if constrained to their original orientations, the COs substantially increase the cationic permeation free energy; with or without water present, CO reorientation is crucial for ion-CO interaction to lower cation free energy barriers; the translocation free energy profiles for potassium-, rubidium-, and cesium-like cations exhibit no broad barriers; the lipid-bound peptide interacts more effectively with anions than cations; anionic translocation free energy profiles exhibit well defined maxima. Using experimental data to estimate transfer free energies of ions and water from bulk electrolyte to a non-polar dielectric (continuum lipid), we found reasonable ion permeation profiles; cations bind and permeate, whereas anions cannot enter the channel. Cation selectivity arises because, for ions of the same size and charge, anions bind hydration water more strongly.