Zhou Y , Lingle CJ .

GM066215 NIGMS NIH HHS , R01 GM066215 NIGMS NIH HHS

	Figure 1. Channels that activate in the presence of paxilline gate with normal voltage dependence and kinetics. (A) G-V curves were normalized to the maximal conductance observed in control saline. Currents were activated with 10 µM cytosolic Ca2+ from a holding potential of 0 mV. For prepaxilline, Vh = 16.31 ± 0.15 mV (z = 0.87 ± 0.01 e); in 100 nM paxilline, Vh = 24.75 ± 0.13 mV (z = 0.86 ± 0.01 e); and, after washout of paxilline, Vh = 28.0 ± 0.19 mV (z = 0.88 ± 0.01 e). (B) G-V curves from A were normalized to the fitted maximum for each condition to highlight the lack of G-V shift. (C) G-V curves were generated in the presence and absence of paxilline, but with all solutions containing 10 mM DTT (n = 7 patches). For control saline, Vh = 25.04 ± 1.2 mV (z = 0.86 ± 0.06 e); with 50 nM paxilline, Vh = 21.21 ± 1.85 (z = 0.79 ± 0.07 e); and after wash, Vh = 28.65 ± 9.0 (z =1.13 ± 0.05 e). (D) The same G-V curves in C are normalized to the maximal conductance in each case to highlight their similarity. (E) 2-ms steps to 160 mV were applied at 0.2 Hz to monitor BK activation with 300 µM Ca2+, while holding the patch at −80 mV. The application of 100 nM paxilline results in slow diminution of BK current with a time constant (fitted red line) of 9.6 ± 1.1 s. (F) For the same patches as in E, steps to 160 mV with 300 µM Ca2+ were used to monitor recovery from paxilline inhibition, with recovery at 300 µM Ca2+ at −80 mV with the indicated recovery time constant (red line). (G) For a single patch, BK current activation (closed circles) was monitored at 160 mV and deactivation (open circles) at −80 mV with 300 µM Ca2+ before and during the application of 20 nM paxilline, showing that paxilline does not alter the kinetics of channels that open and close in the presence of paxilline. (H) A patch was held at 0 mV and 500 nM paxilline was applied at either of two different Ca2+ concentrations (10 or 100 µM). The onset of paxilline block is more rapid with 10 µM Ca2+.
	Figure 2. Block by paxilline exhibits an inverse dependence on Po, but no dependence on Ca2+ per se. G-V curves were generated under three equilibration conditions (A: 10 µM Ca2+, 0 mV; B: 300 µM Ca2+, 0 mV; C: 300 µM, −70 mV), with either control saline or either of two paxilline concentrations, 10 or 100 nM. For all patches included in this dataset, each patch was examined under all conditions. Paxilline was applied for 4 min before generation of G-V curves. Among different patches, the sequence of holding conditions was varied. G-V curves were normalized to the maximal conductance observed in the absence of paxilline under each holding condition. Curves to control points are fitted single Boltzmann functions, whereas curves in the presence of paxilline have no significance. (D) The fractional block for voltages from 40 to 120 mV was determined for each paxilline application under the three conditions and plotted in relation to the Po at the holding condition defined by the fitted Boltzmann. For 10 µM Ca2+ and 0 mV, the effective Po was 0.02; for 300 µM and −70 mV, the Po was 0.07; and for 300 µM Ca2+ and 0 mV, the Po at the holding condition was 0.48.
	Figure 3. Paxilline inhibits channels at conditions of low Po, but not under conditions of high Po. (A) An inside-out patch bathed with 300 µM Ca2+ was initially held at −80 mV. The patch potential was then stepped to holding potentials of −40, 0, 40, and 80 mV (from left to right), and 1.6-ms steps to 160 mV were used to monitor available BK current, while 100 nM paxilline was applied after the 10th step at a given holding potential. Paxilline was washed out and full recovery from block was obtained between tests at different holding potentials. At the most negative potentials, block is substantial, whereas at 40 and 0 mV, there is little development of block. (B) The peak outward current from the traces in A is plotted as a function of elapsed experimental time. (C) The time course of reduction of current during sustained depolarization to 80 mV is shown, establishing that the reduction of current at the positive holding potentials (B) does not reflect paxilline block, but an intrinsic slow reduction in BK conductance with prolonged depolarization. (D) All traces are from the same single-channel patch, stimulated with the protocol shown on the top. The patch was constantly exposed to 300 µM cytosolic Ca2+. (1) Control activity in the absence of paxilline. (2) The holding potential was changed to −70 mV, and 100 nM paxilline was applied. The trace was taken after 30 s in paxilline. (3) The trace was taken ∼30 s after the patch had been returned to 70 mV while in the constant presence of 100 nM paxilline. (4) The trace was taken ∼30 s after the patch was again returned to −70 mV while in paxilline. (5) The trace was obtained after washout of paxilline while holding the patch at 70 mV. (6) The trace was taken ∼30 s after 100 nM paxilline was applied while holding at 70 mV.
	Figure 4. Essentially complete recovery from paxilline block can occur, even in the continuous presence of paxilline under conditions of high Po. (A) The indicated test-pulse sequence was applied every 1 s while holding at −80 mV with 300 µM Ca2+. The traces show before paxilline application, after ∼50% inhibition by paxilline, and during the full paxilline effect. (B) For the same patch in A, the equilibration conditions were altered to 80 mV with 300 µM Ca2+ while still in the continuous presence of 100 nM paxilline. Brief sojourns to −80 mV with test steps to 160 mV were used to monitor recovery in the presence of paxilline. A 60-s washout of paxilline confirmed that no additional recovery occurred. (C) The time course of onset and recovery from inhibition by 100 nM paxilline, while in the continuous presence of paxilline, is plotted for the cell shown in A and B, with the numbers corresponding to the approximate times of the traces in A and B.
	Figure 5. Paxilline reduces NPo at conditions where voltage sensors are largely inactive, and does not influence the voltage-sensor equilibrium. (A; top) The trace shows example channel activity at −80 mV and 300 µM Ca2+ for a macropatch with many channels. 4-ms steps to 100 mV (not depicted) were also used to monitor paxilline inhibition. (Middle and bottom) These traces show activity under the same conditions but with 5 and 100 nM paxilline, respectively. NPo was determined from activity at −80 mV. (B) The NPo measured in paxilline for 3 s of activity normalized by the NPo measured in the absence of paxilline is plotted as a function of paxilline. The solid line corresponds to a fit of NPo(pax)/NPo=11+([PAX]IC50)n, with IC50 = 5.5 ± 1.1 nM with n = 1. Red dotted line corresponds to a fit of the same function with n = 2. (C) Gating currents measured with an activation step to 160 mV from −80 mV with 0 µM Ca2+ are shown in the absence and presence of 500 nM paxilline. (D) The Qon integrated over 1 ms for steps to the indicated potentials are plotted for control and 500-nM paxilline solutions. Fitted lines correspond to: without paxilline, z = 0.56 ± 0.050 e with Vh = 137.6 ± 14.3 mV; with paxilline, z = 0.54 ± 0.025 e with Vh = 131.4 ± 2.1 mV. (E) Qoff is plotted as a function of previous command potential for 0 and 500 nM paxilline. Without paxilline, z = 0.66 ± 0.07 e with Vh = 142.7 ± 14.3 mV; with paxilline, z = 0.56 ± 0.035 e with Vh = 130.2 ± 9.1 mV.
	Figure 6. Concentration dependence of paxilline inhibition at four different conditions of channel Po. (A) Traces show currents activated by brief steps to 160 mV under equilibration conditions of −70 mV and 300 µM Ca2+ with 5, 20, 50, and 200 nM paxilline. Red line shows the identical level of peak current for each paxilline test. (B) Traces show currents activated by steps to 160 mV under equilibration conditions of 40 mV and 300 µM Ca2+ for 200 nM, 500 nM, and 5 µM paxilline, all from the same patch. (C) The onset of inhibition of current activated at 160 mV with 300 µM Ca2+ at −70-mV equilibration condition from traces as in A is shown for five paxilline concentrations along with single-exponential fits (red). (D) Onset of inhibition with single-exponential fits (red) is shown for the higher Po equilibrium condition (B). (E) The fraction of unblocked BK current is plotted as a function of paxilline for four different equilibration conditions (−70, 0, 40, and 70 mV, all with 300 µM Ca2+) from experiments as in A and B. Dotted red lines correspond to fits of a Hill function, with IC50 values of 11.7 ± 1.9 nM, 58.4 ± 2.9 nM, 469.8 ± 94.9 nM, and 5.37 ± 1.0 µM, from left to right. Solid lines correspond to the fit of Scheme 1, with Kp = 11.85 nM and Ep = 0.002, with n = 1.09. (F) The inhibition of NPo at −80 mV and either 10 or 300 µM Ca2+ is displayed from Fig. 5 B, with the dotted red line corresponding to the best fit from Scheme 1 (E) (Kp = 11.85 nM). (G) IC50s from E are plotted as a function of O/C and fit with log(IC50) = m(O/C) + log(Kcp), where m (0.33 ± 0.02) is the slope of the relationship and Kp (12.1 ± 1.1 nM) is the extrapolated IC50 with all channels closed. This provides a model-independent estimate of paxilline inhibition of closed channels. (H) IC50 estimates are replotted as a function of Po along with the fit in F. The extrapolation of the line to Po of ∼1 provides a model-independent estimate of paxilline inhibition of open channels.
	Figure 7. Paxilline stabilizes closed states with only weak, if any, binding to open states. (A) Curves of concentration-dependent inhibition of BK current at four equilibration conditions were fit with Scheme 1, with the assumption that the current activated at positive potentials reflects channels initially either in C, O, or OB, i.e., any open channels with bound paxilline are conducting. Each panel from left to right corresponds to fits with Scheme 1 (Eq. 7) in which either one, two, or four paxilline molecules can bind to inhibitory positions. Best-fit values are given in the figure. The model with n = 1 best accounts for the shape of the inhibition by paxilline. (B; left) Scheme 1 was again used, while constraining Ep to 0.01 (left), 0.1 (middle), or 1.0 (right), showing that increasing open-state affinity fails to account for the data. Right-hand panel corresponds to state-independent paxilline interaction with C and O. (C) Ep was set to 0, thereby approximating strictly closed-channel block. (D) Data were fit with Scheme 3 (Eq. 3) in which the paxilline-bound open state is nonconducting. On the left, the value for Ep drifted toward 0, similar to a strictly closed-channel block situation. On the right, Ep was set to 1 (state-independent binding of paxilline). SSQN in A and C corresponds to the sum-of-squares for a given fit normalized to the sum-of-squares for the left panel in A.
	Figure 8. Kinetics of block onset is more reliably estimated by step changes in equilibration conditions while in the constant presence of paxilline rather than by wash-in of paxilline. (A) Onset of paxilline is compared at −80 mV and 300 µM Ca2+ for two situations: first, simple perfusion of 100 nM paxilline over the cytosolic face of the face, and second, a change in equilibration conditions from 80 to −80 mV. Voltage protocols in each case are shown schematically. Available BK current was monitored by a 2-ms step to 160 mV applied at 0.5 Hz. Symbols over the voltage steps for a particular protocol correspond to the particular symbols showing the onset of block as a function of elapsed time, with single-exponential time constants as given. (B) Estimates of time constants from individual patches for each method of assessing paxilline block are shown along with means and STD. Each method was evaluated with the same patches. An F-test provided an assessment of whether variance for each set of estimates was significantly different.
	Figure 9. Paxilline inhibition is faster at higher closed-channel probabilities. (A) All traces were obtained from the same patch with the indicated voltage protocol while in the continuous presence of 100 nM paxilline and 300 µM Ca2+. Black traces correspond to currents activated after a re-equilibration period at 80 mV (with 300 µM Ca2+), whereas red traces are the final trace after a change to a new equilibration voltage (as indicated). (B) The onset of current inhibition from the examples in A is plotted as a function of time at the new equilibration potentials. Red lines are single-exponential fits to the onset of inhibition. (C) Onset of inhibition at intermediate Pc is better fit with two (blue) exponential components than one (red). (D) The rate of block (means, SEMs, and individual estimates) from experiments as in B is plotted as a function of Pc, with Pc calculated from the G-V curves at 300 µM Ca2+. Closed red symbols correspond to the faster rate resulting from the fit of either one or two exponential components to the onset time course in B and C. (E and F) Onset of inhibition at −80 mV (E) and −100 mV (F) is shown for different paxilline concentrations along with single-exponential fits. (G) Blocking rate is plotted as a function of [paxilline]. The fitted red line has a slope of 2.1 × 106 M−1s−1. Each dotted line connects determinations at different [paxilline] for single patches.
	Figure 10. Recovery from paxilline inhibition is faster at higher Po. (A) Unblock time constant from washout of paxilline is comparable to unblock during change in equilibration conditions. The panels are all from the same patch, with the unblocking time course examined at 0 (top), 40 (middle), or 80 mV (bottom). Black symbols and fitted line correspond to unblock in the constant presence of 100 nM paxilline after a change in equilibration condition from −80 mV, 300 µM Ca2+ to each of the three voltages. Red symbols and fitted red lines correspond to washout of paxilline at the indicated voltage with 300 µM Ca2+. BK availability was assessed with brief test steps to 160 mV. Po during the recovery conditions was estimated from G-V curves as 0.7 (0 mV, top), ∼0.85 (40 mV, middle), and ∼0.9 (80 mV, bottom). (B) Recovery time course was compared in the same patch for washout of paxilline at 0 (Po of ∼0.7), −40 (Po of ∼0.4), and −80 mV (Po of ∼0.1), all in 300 µM Ca2+. (C) Recovery time course from A (middle) for washout of paxilline is plotted on a logarithmic scale along with fits of an exponential of form I(t) = (1 − exp(−t/tau)n, for n = 1, 2, or 4. (D) Open circles show recovery time constants for patches examined as in A, with closed symbols corresponding to time constants measured during paxilline washout, and open circles corresponding to the constant presence of paxilline, with each point reflecting the mean of at least four patches. Closed diamonds correspond to time constants measured as in B. The fitted G-V curve (Vh = −34.0 mV; z = 0.98) for currents activated in the patches in A and B is shown to highlight the extent of changes in fractional activation for the different recovery conditions. Red symbols correspond to seven patches for which recovery was measured at 0 mV in the constant presence of either 100 nM paxilline (red square) or 20 nM paxilline (red circle).
	Figure 11. Manipulation of BK Po by MTS modification of S6 residues also modulates paxilline sensitivity. (A) Traces on the top show that 100 nM paxilline readily blocks Slo1-A313C currents, but after modification of A313C with MTSET, paxilline produces hardly any block of the residual current. (B) The normalized conductances from the experiment shown in A are plotted for A313C in the absence and presence of paxilline, and then after modification by MTSET. Slo1-A313C-MTSET is constitutively active over the potentials examined. (C) Results are shown for Slo1-A313C before and after modification by MTSEA. Modification by MTSEA produces less G-V shift than for modification by MTSET, whereas block by paxilline is also intermediate. (D) Similar results are shown for Slo1-A313C before and after modification by MTSES. MTSES produces only modest shifts in the BK G-V and has little effect on block by paxilline.
	Figure 12. bbTBA and sucrose each slow paxilline inhibition. (A) Blockade of Slo1 current by 100 nM paxilline is displayed with and without simultaneous application of 100 µM bbTBA. The equilibration conditions were 0 mV with 10 µM Ca2+, and BK current availability was monitored by voltage steps to 160 mV applied at 1 Hz. Blocker applications are shown with horizontal bars, with all measurements from the same patch. Block and unblock with 100 µM bbTBA alone (black) is rapid, whereas block by 100 nM paxilline (red) alone exhibits slow onset and recovery. After simultaneous application of paxilline with 100 µM bbTBA, the amount of paxilline inhibition is reduced about half. (B) BK currents were activated with 300 µM Ca2+ with the indicated voltage protocol without and with the addition of 2 M sucrose to the cytosolic solution. Insets show currents with a red trace at −20 mV. Sucrose markedly reduces outward current, whereas tail currents at −120 mV are reduced a little more than half. For control solutions, Vh = −16.3 ± 7.2 mV, whereas with 2 M sucrose, Vh = −12.8 ± 3.3 mV. (C) 100 nM paxilline strongly inhibits BK current, whereas in 2 M sucrose, both outward and inward currents are only slightly affected by paxilline. Top traces are single sweeps. Bottom traces correspond to an average of 15 sweeps before, during, and after washout of 100 nM paxilline. (D) Plot of time course of paxilline inhibition without and with 2 M sucrose suggests that sucrose slows the development of inhibition by paxilline.
	Figure 13. Paxilline does not hinder MTSET modification of A313C. (A; top) The traces show currents activated with 300 µM Ca2+ at voltage steps up to 200 mV for channels arising from Slo1-C430S-A313C. (Bottom) Currents were similarly elicited, but after 120 s of application of 1 mM MTSET while holding the patch at −80 mV with 0 Ca2+. (B; top) The traces show current for Slo1-C405A-A313C activated with 300 µM Ca2+. The patch was then first perfused with 500 nM paxilline for 100 s while holding at −80 mV with 0 Ca2+, and then exposed to 1 mM MTSET with 500 nM paxilline for 120 s while still at −80 mV with 0 Ca2+. (C) G-V curves summarize results from patches examined for conditions shown in A and B. Because MTSET modification was tested both without and with paxilline, two separate sets of control G-V curves at 300 µM Ca2+ are shown. (D) BK currents were recorded in 300 µM Ca2+ before (left) and after (top right) modification by 1 mM MTSET, applied for 120 s in 0 Ca2+ at −80 mV. Modification is similar to that in A. The patch was then held at 0 mV, 0 Ca2+, and then channels were opened by 20 100-msec steps to 160 mV, after which the traces on the bottom right were obtained in 300 µM Ca2+. (E) G-V curves correspond to conditions as in D for control, after closed-state modification by 1 mM MTSET, and then after subsequent open-state modification by the same MTSET solution.
	Figure 14. Cartoons describing possible views of inhibition of closed BK channels by paxilline. (A) Schematic BK channels are either closed (left pair) or open (right pair). The channels are diagrammed with an opening at the cytosolic end of the channel, which allows small molecules in and out of the inner cavity. Paxilline occludes the aperture to the inner cavity in the closed BK channel. Binding of paxilline to the closed channel (bottom left) occludes the aperture to the inner cavity. The open conformation either is unable to bind paxilline or does so with low affinity, without any occlusion of ion permeation. Dotted arrows indicate transitions that are either very low probability or do not occur. (B) Overall scheme is the same as in A, except for positions of inner-pore helices along alternative aqueous pathways for access of small molecules to the inner cavity. Thus, occlusion of the closed-channel aperture by paxilline may not impede access of small molecules to the inner cavity, such that MTS reagents can modify position A313C.

Adams, Drug blockade of open end-plate channels. 1976, Pubmed

Adams, Drug blockade of open end-plate channels. 1976, Pubmed
Anderson, Charybdotoxin block of single Ca2+-activated K+ channels. Effects of channel gating, voltage, and ionic strength. 1988, Pubmed
Armstrong, The inner quaternary ammonium ion receptor in potassium channels of the node of Ranvier. 1972, Pubmed
Armstrong, Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons. 1969, Pubmed
Banerjee, Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel. 2013, Pubmed
Brelidze, Probing the geometry of the inner vestibule of BK channels with sugars. 2005, Pubmed , Xenbase
Bruhova, Access and binding of local anesthetics in the closed sodium channel. 2008, Pubmed
Bush, Bioprotective Alkaloids of Grass-Fungal Endophyte Symbioses. 1997, Pubmed
Chen, Charge substitution for a deep-pore residue reveals structural dynamics during BK channel gating. 2011, Pubmed
Chen, BK channel opening involves side-chain reorientation of multiple deep-pore residues. 2014, Pubmed
Choi, The internal quaternary ammonium receptor site of Shaker potassium channels. 1993, Pubmed , Xenbase
Choi, Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels. 1991, Pubmed
DiChiara, Redox modulation of hslo Ca2+-activated K+ channels. 1997, Pubmed , Xenbase
Doyle, The structure of the potassium channel: molecular basis of K+ conduction and selectivity. 1998, Pubmed
Essin, BK channels in innate immune functions of neutrophils and macrophages. 2009, Pubmed
Flynn, A cysteine scan of the inner vestibule of cyclic nucleotide-gated channels reveals architecture and rearrangement of the pore. 2003, Pubmed
Fodor, Tetracaine reports a conformational change in the pore of cyclic nucleotide-gated channels. 1997, Pubmed , Xenbase
Fodor, Mechanism of tetracaine block of cyclic nucleotide-gated channels. 1997, Pubmed , Xenbase
Gross, Agitoxin footprinting the shaker potassium channel pore. 1996, Pubmed , Xenbase
Han, Conus venoms - a rich source of peptide-based therapeutics. 2008, Pubmed
Hanck, Using lidocaine and benzocaine to link sodium channel molecular conformations to state-dependent antiarrhythmic drug affinity. 2009, Pubmed
Hille, Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. 1977, Pubmed
Horrigan, Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels. 2002, Pubmed , Xenbase
Horrigan, Allosteric voltage gating of potassium channels II. Mslo channel gating charge movement in the absence of Ca(2+). 1999, Pubmed
Imlach, Structural determinants of lolitrems for inhibition of BK large conductance Ca2+-activated K+ channels. 2009, Pubmed
Imlach, Mechanism of action of lolitrem B, a fungal endophyte derived toxin that inhibits BK large conductance Ca²+-activated K+ channels. 2011, Pubmed
Jiang, The open pore conformation of potassium channels. 2002, Pubmed
Jiang, Crystal structure and mechanism of a calcium-gated potassium channel. 2002, Pubmed
Knaus, Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. 1994, Pubmed
Lee, A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom. 2004, Pubmed
Lee, Interaction between extracellular Hanatoxin and the resting conformation of the voltage-sensor paddle in Kv channels. 2003, Pubmed , Xenbase
Lenaeus, Structural basis of TEA blockade in a model potassium channel. 2005, Pubmed
Liang, Proteome and peptidome profiling of spider venoms. 2008, Pubmed
Lingle, Anomalous voltage dependence of channel blockade at a crustacean glutamate-mediated synapse. 1989, Pubmed
Long, Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. 2005, Pubmed
MacKinnon, Mechanism of charybdotoxin block of the high-conductance, Ca2+-activated K+ channel. 1988, Pubmed
Magidovich, Conserved gating hinge in ligand- and voltage-dependent K+ channels. 2004, Pubmed , Xenbase
Meera, A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin. 2000, Pubmed , Xenbase
Milescu, Interactions between lipids and voltage sensor paddles detected with tarantula toxins. 2009, Pubmed
Muroi, Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel. 2009, Pubmed , Xenbase
Narahashi, Tetrodotoxin derivatives: chemical structure and blockage of nerve membrane conductance. 1967, Pubmed
NARAHASHI, TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS. 1964, Pubmed
Neher, Local anaesthetics transiently block currents through single acetylcholine-receptor channels. 1978, Pubmed
Perozo, Structural rearrangements underlying K+-channel activation gating. 1999, Pubmed
Raffaelli, BK potassium channels control transmitter release at CA3-CA3 synapses in the rat hippocampus. 2004, Pubmed
Sanchez, Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel. 1996, Pubmed , Xenbase
Shao, The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells. 1999, Pubmed
Smith, Purification of charybdotoxin, a specific inhibitor of the high-conductance Ca2+-activated K+ channel. 1986, Pubmed
Swartz, Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels. 1997, Pubmed
Swartz, Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites. 1997, Pubmed , Xenbase
Tammaro, Pharmacological evidence for a key role of voltage-gated K+ channels in the function of rat aortic smooth muscle cells. 2004, Pubmed
Tang, Closed-channel block of BK potassium channels by bbTBA requires partial activation. 2009, Pubmed , Xenbase
Uysal, Crystal structure of full-length KcsA in its closed conformation. 2009, Pubmed
Wang, Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor. 2011, Pubmed
Wilkens, State-independent block of BK channels by an intracellular quaternary ammonium. 2006, Pubmed , Xenbase
Xia, Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells. 1999, Pubmed , Xenbase
Xia, Rectification and rapid activation at low Ca2+ of Ca2+-activated, voltage-dependent BK currents: consequences of rapid inactivation by a novel beta subunit. 2000, Pubmed , Xenbase
Yifrach, Energetics of pore opening in a voltage-gated K(+) channel. 2002, Pubmed , Xenbase
Zhang, Cysteine modification alters voltage- and Ca(2+)-dependent gating of large conductance (BK) potassium channels. 2005, Pubmed
Zhang, Allosteric regulation of BK channel gating by Ca(2+) and Mg(2+) through a nonselective, low affinity divalent cation site. 2001, Pubmed , Xenbase
Zhou, Cysteine scanning and modification reveal major differences between BK channels and Kv channels in the inner pore region. 2011, Pubmed , Xenbase
Zhou, Glycine311, a determinant of paxilline block in BK channels: a novel bend in the BK S6 helix. 2010, Pubmed , Xenbase
Zhou, Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. 2001, Pubmed , Xenbase