Functional and molecular analysis of transient voltage‐dependent K
            +
            currents in rat hippocampal granule cells

Two novel toxins were purified from the venom of the Mexican scorpion Centruroides limpidus limpidus, using an immunoassay based on antibodies raised against noxiustoxin (NTX), a known K(+)-channel-blocker-peptide. The primary structure of C. l. limpidus toxin 1 was obtained by Edman degradation and was shown to be composed of 38 amino acid residues, containing six half-cystines. The first 36 residues of C. l. limpidus toxin 2 were also determined. Both toxins are capable of displacing the binding of radio-labelled NTX to rat brain synaptosomes with high affinity (about 100 pM). These toxins are capable of inhibiting transient K(+)-currents (resembling IA-type currents), in cultured rat cerebellar granule cells. About 50% of the peak currents are reduced by application of a 1.5 microM solution of toxins 1 and 2 The K+ current reduction is partially reversible, under washing but not voltage-dependent. Comparison of the primary structure of C. l. limpidus toxin 1 with other known toxins shows 74% identity with margatoxin, 64% with NTX, 51% with kaliotoxin, 39% with iberiotoxin, 37% with charybdotoxin and Lq2, and 29% with leirutoxin 1. The only invariant amino acids in all these toxins are the six cysteines, a glycine in position 26 and two lysines at positions 28 and 33, respectively. The relevance of these differences in terms of possible structure-function relationships is discussed.

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Molecular and pharmacological characteristics of transient voltage-dependent K+ currents in cultured human pulmonary arterial smooth muscle cells

British Journal of Pharmacology ◽

10.1038/sj.bjp.0706285 ◽

2005 ◽

Vol 146 (1) ◽

pp. 49-59 ◽

Cited By ~ 10

Author(s):

Haruko Iida ◽

Taisuke Jo ◽

Kuniaki Iwasawa ◽

Toshihiro Morita ◽

Hisako Hikiji ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Arterial Smooth Muscle ◽

Voltage Dependent ◽

Pulmonary Arterial ◽

Arterial Smooth Muscle Cells ◽

Pulmonary Arterial Smooth Muscle ◽

Transient Voltage ◽

K Currents

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Non-genomic action of ovarian steroid hormones on a transient voltage-dependent K+ current in human luteinised granulosa cells

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2004-819053 ◽

2004 ◽

Vol 112 (S 1) ◽

Author(s):

L Kunz ◽

A Krieger ◽

R Rämsch ◽

A Mayerhofer

Keyword(s):

Steroid Hormones ◽

Granulosa Cells ◽

Ovarian Steroid ◽

Voltage Dependent ◽

K Current ◽

Transient Voltage

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Voltage-dependent k+ currents in rat cardiac dorsal root ganglion neurons

Neuroscience ◽

10.1016/s0306-4522(03)00124-6 ◽

2003 ◽

Vol 119 (1) ◽

pp. 181-191 ◽

Cited By ~ 9

Author(s):

R. Rola ◽

G. Witkowski ◽

P.J. Szulczyk

Keyword(s):

Dorsal Root Ganglion ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

Voltage Dependent ◽

Ganglion Neurons ◽

K Currents

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Gonadotropin-Releasing Hormone Inhibits Ether-à-Go-Go-Related Gene K+ Currents in Mouse Gonadotropes

Endocrinology ◽

10.1210/en.2009-0718 ◽

2010 ◽

Vol 151 (3) ◽

pp. 1079-1088 ◽

Cited By ~ 5

Author(s):

Wiebke Hirdes ◽

Crenguta Dinu ◽

Christiane K. Bauer ◽

Ulrich Boehm ◽

Jürgen R. Schwarz

Keyword(s):

Resting Potential ◽

Related Gene ◽

Activation Curve ◽

Signal Cascade ◽

Primary Mouse ◽

Voltage Dependent ◽

K Current ◽

Unknown Signal ◽

Ca2 Channels ◽

K Currents

Secretion of LH from gonadotropes is initiated by a GnRH-induced increase in intracellular Ca2+ concentration ([Ca2+]i). This increase in [Ca2+]i is the result of Ca2+ release from intracellular stores and Ca2+ influx through voltage-dependent Ca2+ channels. Here we describe an ether-à-go-go-related gene (erg) K+ current in primary mouse gonadotropes and its possible function in the control of Ca2+ influx. To detect gonadotropes, we used a knock-in mouse strain, in which GnRH receptor-expressing cells are fluorescently labeled. Erg K+ currents were recorded in 80–90% of gonadotropes. Blockage of erg currents by E-4031 depolarized the resting potential by 5–8 mV and led to an increase in [Ca2+]i, which was abolished by nifedipine. GnRH inhibited erg currents by a reduction of the maximal erg current and in some cells additionally by a shift of the activation curve to more positive potentials. In conclusion, the erg current contributes to the maintenance of the resting potential in gonadotropes, thereby securing a low [Ca2+]i by restricting Ca2+ influx. In addition, the erg channels are modulated by GnRH by an as-yet unknown signal cascade.

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Differential Oxidative Modulation of Voltage-Dependent K+ Currents in Rat Hippocampal Neurons

Journal of Neurophysiology ◽

10.1152/jn.2002.87.6.2990 ◽

2002 ◽

Vol 87 (6) ◽

pp. 2990-2995 ◽

Cited By ~ 42

Author(s):

Wolfgang Müller ◽

Katrin Bittner

Keyword(s):

Hydrogen Peroxide ◽

Hippocampal Neurons ◽

Immune Defense ◽

Delayed Rectifier ◽

Delayed Rectifier Current ◽

Cell Recording ◽

Voltage Dependent ◽

Steady State Inactivation ◽

K Currents ◽

Stimulation Of

Oxidative stress is enhanced by [Ca2+]i-dependent stimulation of phospholipases and mitochondria and has been implicated in immune defense, ischemia, and excitotoxicity. Using whole cell recording from hippocampal neurons, we show that arachidonic acid (AA) and hydrogen peroxide (H2O2) both reduce the transient K+ current I A by −54 and −68%, respectively, and shift steady-state inactivation by −10 and −15 mV, respectively. While AA was effective at an extracellular concentration of 1 μM and an intracellular concentration of 1 pM, extracellular H2O2 was equally effective only at a concentration >800 μM (0.0027%). In contrast to AA, H2O2 decreased the slope of activation and increased the slope of inactivation of I A and reduced the sustained delayed rectifier current I K(V) by 22% and shifted its activation by −9 mV. Intracellular application of the antioxidant glutathione (GSH, 2–5 mM) blocked all effects of AA and the reduction of I A by H2O2. In contrast, intracellular GSH enhanced reduction of I K(V) by H2O2. Decrease of the slope of activation and increase of the slope of inactivation of I A by hydrogen peroxide was blocked and reversed to a decrease, respectively, by intracellular application of GSH. Intracellular GSH did not prevent H2O2 to shift inactivation and activation of I A and activation of I K(V) to more negative potentials. We conclude, that AA and H2O2modulate voltage-activated K currents differentially by oxidation of GSH accessible intracellular and GSH inaccessible extracellular K+-channel domains, thereby presumably affecting neuronal information processing and oxidative damage.

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