Electrically gated ionic channels in lipid bilayers

Ehrenstein, Gerald; Lecar, Harold

doi:10.1017/s0033583500000123

Cited by 351 publications

(221 citation statements)

References 63 publications

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“…3). In our previous study, we proposed a membrane discrimination mechanism for a-helical antimicrobial peptides whose sole target is the biomembrane (26), based on a barrel-stave mechanism (27) in eukaryotic cells and a carpet mechanism (7) in prokaryotic cells. We believe that a-helical peptide forms pores or channels in eukaryotic cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Studies on Mechanism of Action of Anticancer Peptides by Modulation of Hydrophobicity Within a Defined Structural Framework

Huang

Wang

et al. 2011

Molecular Cancer Therapeutics

173

129

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In the present study, the hydrophobicity of a 26-residue a-helical peptide (peptide P) was altered to study the effects of peptide hydrophobicity on the mechanism of action of cationic anticancer peptides. Hydrophobicity of the nonpolar face of the peptides was shown to correlate with peptide helicity. The self-association ability of peptides in aqueous environment, determined by the reversed-phase high performance liquid chromatography temperature profiling, showed strong influence on anticancer activity. The peptide analogues with greater hydrophobicity showed stronger anticancer activity determined by IC 50 values with a necrotic-like membrane disruption mechanism. Peptide analogues exhibited high specificity against cancer cells and much higher anticancer activity than widely-used anticancer chemical drugs. The mechanism of action of anticancer peptides was also investigated.

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Section: Discussionmentioning

confidence: 99%

Studies on Mechanism of Action of Anticancer Peptides by Modulation of Hydrophobicity Within a Defined Structural Framework

Huang

Wang

et al. 2011

Molecular Cancer Therapeutics

173

129

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“…4, should be bell-shaped functions of membrane potential with a peak at VT (Hodgkin & Huxley, 1952;Ehrenstein & Lecar, 1977). Examination of the relaxations illustrated in Figs.…”

Section: Inward Rectification In Sensory Neurones Kinetic Behaviour Omentioning

confidence: 98%

A voltage‐clamp analysis of inward (anomalous) rectification in mouse spinal sensory ganglion neurones.

Mayer

Westbrook

1983

The Journal of Physiology

426

320

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SUMMARY1. Mouse embryo dorsal root ganglion neurones were grown in tissue culture and voltage-clamped with two micro-electrodes. Hyperpolarizing voltage commands from holding potentials of -50 to -60 mV evoked slow inward current relaxations which were followed by inward tail currents on repolarization to the holding potential. These relaxations are due to the presence of a time-and voltage-dependent conductance provisionally termed Gh.2. Gh activates over the membrane potential range -60 to -120 mV. The presence of Gh causes time-dependent rectification in the current-voltage relationship measured between -60 and --120 mV. Gh does not inactivate within this range and thus generates a steady inward current at hyperpolarized membrane potentials.3. The current carried by Gh increases when the extracellular K+ concentration is raised, and is greatly reduced in Na+-free solutions. Current-voltage plots show considerably less inward rectification in Na+-free solution; conversely inward rectification is markedly enhanced when the extracellular K+ concentration is raised. The reversal potential of 'h is close to -30 mV in media of physiological composition.Tail-current measurement suggests that Ih is a mixed Na+-K+ current.4. Low concentrations ofCs+ reversibly block Ih and produce outward rectification in the steady-state current-voltage relationship recorded between membrane potentials of -60 and -120 mV. Cs+ also reversibly abolishes the sag and depolarizing overshoot that distort hyperpolarizing electrotonic potentials recorded in currentclamp experiments.5. Impermeant anion substitutes reversibly block Ih; this block is different from that produced by Cs+ or Na+-free solutions: Cs+ produces outward rectification in the steady-state current-voltage relationship recorded over the Ih activation range; in Na+-free solutions inward rectification, of reduced amplitude, can still be recorded since Ih is a mixed Na+-K+ current; in anion-substituted solutions the current-voltage relationship becomes approximately linear.6. It is concluded that in dorsal root ganglion neurones anomalous rectification is generated by the time-and voltage-dependent current Ih. The possible function of Ih in sensory neurones is discussed.

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“…In the barrel-stave model (Ehrenstein and Lecar, 1977), peptides reorient perpendicularly to the surface of the membrane and are positioned as the "staves" in a "barrel"-shaped aggregation, with the hydrophobic regions of peptides associating with the hydrophobic core of membrane, while the hydrophilic regions face each other and form an aqueous pore or channel. The formation of pore or channel is a dynamic process.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Recently, based on the "barrel-stave" model (Ehrenstein and Lecar, 1977) and the "carpet" model (Shai, 1999), Chen et al proposed a "membrane discrimination" model for AMPs whose sole target is the biomembrane (Fig. 3) (Chen et al, 2006(Chen et al, , 2007.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Alpha-helical cationic antimicrobial peptides: relationships of structure and function

2010

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Antimicrobial peptides (AMPs), with their extraordinary properties, such as broad-spectrum activity, rapid action and difficult development of resistance, have become promising molecules as new antibiotics. Despite their various mechanisms of action, the interaction of AMPs with the bacterial cell membrane is the key step for their mode of action. Moreover, it is generally accepted that the membrane is the primary target of most AMPs, and the interaction between AMPs and eukaryotic cell membranes (causing toxicity to host cells) limits their clinical application. Therefore, researchers are engaged in reforming or de novo designing AMPs as a 'singleedged sword' that contains high antimicrobial activity yet low cytotoxicity against eukaryotic cells. To improve the antimicrobial activity of AMPs, the relationship between the structure and function of AMPs has been rigorously pursued. In this review, we focus on the current knowledge of α-helical cationic antimicrobial peptides, one of the most common types of AMPs in nature.

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Electrically gated ionic channels in lipid bilayers

Cited by 351 publications

References 63 publications

Studies on Mechanism of Action of Anticancer Peptides by Modulation of Hydrophobicity Within a Defined Structural Framework

Studies on Mechanism of Action of Anticancer Peptides by Modulation of Hydrophobicity Within a Defined Structural Framework

A voltage‐clamp analysis of inward (anomalous) rectification in mouse spinal sensory ganglion neurones.

Alpha-helical cationic antimicrobial peptides: relationships of structure and function

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