Modification of Voltage-Dependent Gating of Potassium Channels by Free Form of Tryptophan Side Chain

Avdonin, Vladimir; Hoshi, Toshinori

doi:10.1016/s0006-3495(01)75683-4

Cited by 11 publications

(7 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the mechanism is not likely to be as specific as those found with aromatic agonists and antagonists of dihydropyridine (DHP)‐sensitive calcium channels [14]. Furthermore, the lack of geometrical specificity suggests that the site is not as restrictive as seen with indole inhibition of Shaker K + but not IRK currents [15]. In both these cases experimental evidence indicates that specific aromatic residues in the protein are important for the effect on channel activity.…”

Section: Discussionmentioning

confidence: 99%

Indole and other aromatic compounds activate the yeast TRPY1 channel

Haynes

Loukin

et al. 2008

FEBS Letters

View full text Add to dashboard Cite

The yeast TRPY1 (Yvc1p) channel is activated by membrane stretch to release vacuolar Ca 2+ into the cytoplasm upon osmotic upshock. Exogenously added indole greatly enhances the upshock-induced Ca 2+ release in vivo. Indole also reversibly activates the channels under patch clamp. A minimum of 10 À6 M Ca 2+ is needed for membrane stretch force to open TPRY1, but indole activation appears to be Ca 2+ independent. A deletion of 30 residues at the predicted cytoplasmic domain, 570-600D, renders TRPY1 insensitive to stretch force upto 10 À3 M Ca 2+ . Nonetheless, indole readily activates this mutant channel. Several other aromatic compounds, e.g. the antimicrobial parabens, also activate TRPY1. These compounds likely alter the innate forces in the lipid bilayer received by the channel.

show abstract

Section: Discussionmentioning

confidence: 99%

Indole and other aromatic compounds activate the yeast TRPY1 channel

Haynes

Loukin

et al. 2008

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…This normalization was necessary as the variability in the estimated absolute open probability values at negative voltages was high, often ranging from 1 × 10 −7 to 2 × 10 −6 at −120 mV on a given day of experiments. Single-channel dwell times were measured as described previously39 and were not corrected for the left-censor time of the recording system.…”

Section: Methodsmentioning

confidence: 99%

Comparative effects of H⁺and Ca²⁺on large-conductance Ca²⁺- and voltage-gated Slo1 K⁺channels

Hou¹,

Horrigan²,

Xu³

et al. 2009

Channels

Self Cite

View full text Add to dashboard Cite

SummaryLarge-conductance Ca 2+ -and voltage-gated Slo1 BK channels are allosterically activated by depolarization and intracellular ligands such as Ca 2+ . Of the two high-affinity Ca 2+ sensors present in the channel, the RCK1 sensor also mediates H + -dependent activation of the channel. In this study, we examined the comparative mechanisms of the channel activation by Ca 2+ and H + . Steady-state macroscopic conductance-voltage measurements as well as single-channel openings at negative voltages where voltage-sensor activation is negligible showed that at respective saturating concentrations Ca 2+ is more effective in relative stabilization of the open conformation than H + . Calculations using the Debye-Hückel formulation suggest that small structural changes in the RCK1 sensor, on the order of few angstroms, may accompany the H + -mediated opening of the channel. While the efficacy of H + in activation of the channel is less than that of Ca 2+ , H + more effectively accelerates the activation kinetics when examined at the concentrations equipotent on macroscopic voltage-dependent activation. The RCK1 sensor therefore is capable of transducing the nature of the ligand bound and transmits qualitatively different information to the channel's permeation gate.

show abstract

“…Nevertheless, related indole-based alkaloids produced by the genus Fischerella are suspected to act as ion channel modulators similar to saxitoxin 38 . Furthermore, the indole moiety itself is a known modulator of voltage-dependent gating of potassium channels 39 . Cyclamides are cyclic oligopeptides produced via the ribosomal pathway and heavily functionalized via post-translational modifications 40 .…”

Section: Discussionmentioning

confidence: 99%

The evolutionary advantage of toxin production among cyanobacteria, the oldest known organisms on Earth

Ramos

Ionescu

Koča

2019

Preprint

View full text Add to dashboard Cite

21 organisms on Earth 22 23Cyanobacteria produce toxic secondary metabolites for reasons hitherto unclear. Using a 24 phylogenetic approach that accounts for the high complexity of biosynthetic gene clusters (full or 25 partial inversions, variable length, different number of genes, non-orthologues), we analyzed the 26 sequences of 76 biosynthetic gene clusters covering 19 cyanotoxins. The phylogenetic tree of 27 biosynthetic gene clusters branches first according to the bioactivity of the toxic metabolite 28 (molecular target in another organism), then according to the chemical class and chemical 29 structure of the secondary metabolite, and finally according to the organism and area of origin. 30The bioactivity of a toxic metabolite can be deduced directly from the nucleotide sequence of the 31 biosynthetic gene cluster, without needing to examine the enzymes themselves or to measure 32 expression levels. Bioactivity may have been the primary driving force behind the diversity of 33 secondary metabolism in cyanobacteria. This genetic machinery evolved to facilitate three 34 specific survival strategies acting separately or in tandem, with dominant cyanobacteria 35 possessing the genetic machinery to support all three strategies. Transmembrane (direct) toxicity 36 targeting ion channels, intracellular (indirect) toxicity targeting cell-cycle regulation, and 37 digestion inhibition targeting proteases may have provided the survival advantage underpinning 38 the evolutionary success of both cyanobacteria and their early symbiotic hosts. 39 40 Keywords: cyanotoxin, evolutionary benefit, bioactivity, phylogenetic analysis 41 42 3 43 Introduction 44 Bioactive secondary metabolites, which are products of pathways not directly involved in 45 growth, development, or reproduction, often serve complex functions that aid survival and 46 increase dominance of an organism in a given ecological niche. Snake venoms are probably the 47 most famous examples of bioactive secondary metabolites, though not nearly the most versatile. 48 Bacteria, fungi, and plants all exhibit an impressive array of secondary metabolites, with 49 cyanobacteria being the earliest organisms to develop such capabilities. Cyanobacteria are 50 unicellular photosynthetic prokaryotes populating marine, fresh-water, and land ecosystems, 51 which drove the rapid oxygenation of Earth's atmosphere and are recognized as the ancestors of 52 plastids 1 . Cyanobacteria continue to exert a crucial environmental impact because they produce 53 about 25% of all carbohydrates on Earth and perform massive nitrogen fixation together with 54 sequestering trace metals and phosphorous from the environment, thus fueling most 55 contemporary food chains. In addition, many cyanobacteria produce unique secondary 56 metabolites (typically, peptides and alkaloids) via non-ribosomal peptide synthesis (NRPS) 57 and/or polyketide synthesis (PKS), with complex environmental, economic, and health impact 2 . 58The exact function of cyanobacterial secondary metabolites remains largely un...

show abstract

Modification of Voltage-Dependent Gating of Potassium Channels by Free Form of Tryptophan Side Chain

Cited by 11 publications

References 27 publications

Indole and other aromatic compounds activate the yeast TRPY1 channel

Indole and other aromatic compounds activate the yeast TRPY1 channel

Comparative effects of H⁺and Ca²⁺on large-conductance Ca²⁺- and voltage-gated Slo1 K⁺channels

The evolutionary advantage of toxin production among cyanobacteria, the oldest known organisms on Earth

Contact Info

Product

Resources

About

Modification of Voltage-Dependent Gating of Potassium Channels by Free Form of Tryptophan Side Chain

Cited by 11 publications

References 27 publications

Indole and other aromatic compounds activate the yeast TRPY1 channel

Indole and other aromatic compounds activate the yeast TRPY1 channel

Comparative effects of H+and Ca2+on large-conductance Ca2+- and voltage-gated Slo1 K+channels

The evolutionary advantage of toxin production among cyanobacteria, the oldest known organisms on Earth

Contact Info

Product

Resources

About

Comparative effects of H⁺and Ca²⁺on large-conductance Ca²⁺- and voltage-gated Slo1 K⁺channels