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

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1079-1088 ◽  
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.

Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons

1989 ◽  
Vol 61 (2) ◽  
pp. 245-256 ◽  
Author(s):  
R. C. Foehring ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Firing Rate ◽  
Voltage Clamp ◽  
Resting Potential ◽  
Constant Current ◽  
Repetitive Firing ◽  
Slow Phase ◽  
Voltage Dependent ◽  
Constant Current Stimulation ◽  
K Current ◽  
K Currents

1. The effects of norepinephrine (NE) and related agonists and antagonists were examined on large neurons from layer V of cat sensorimotor cortex ("Betz cells") were examined in a brain slice preparation using intracellular recording, constant current stimulation and single microelectrode voltage clamp. 2. Application of NE (0.1-100 microM) usually caused a small depolarization from resting potential; hyperpolarizations were rare. Application of NE reversibly reduced rheobase and both the Ca2+- and Na+-dependent portions of the slow afterhyperpolarization (sAHP) that followed sustained firing evoked by constant current injection. The faster Ca2+-dependent medium afterhyperpolarization (mAHP), the fast afterhyperpolarization (fAHP), the action potential, and input resistance were unaffected. 3. The changes in excitability produced by NE application were most apparent during prolonged stimulation. The cells exhibited steady repetitive firing to currents that were formerly ineffective. The slow phase of spike frequency adaptation was reduced selectively and less habituation occurred during repeated long-lasting stimuli. The relation between firing rate and injected current became steeper if firing rate was averaged over several hundred milliseconds. 4. During voltage clamp in TTX, NE application selectively reduced the slow component of Ca2+-mediated K+ current. The faster Ca2+-mediated K+ current was unaffected, as were two voltage-dependent, transient K+ currents, the anomalous rectifier and leakage conductance measured at resting potential. Depolarizing voltage steps in the presence of Cd2+ revealed an apparent time- and voltage-dependent increase of the persistent Na+ current after NE application. The voltage-clamp results suggested ionic mechanisms for all effects seen during constant current stimulation except the depolarization from resting potential. The latter was insensitive to Cd2+ and TTX and occurred without a detectable change in membrane conductance. 5. NE application did not alter Ca2+ spikes evoked in the presence of TTX and 10 mM TEA. Inward Ca2+ currents examined during voltage clamp in TTX (with K+ currents reduced) became slightly larger after NE application. We conclude that NEs reduction of the slow Ca2+-mediated K+ current is not caused by reduction of Ca2+ influx. 6. Effects on membrane potential, rheobase, and the sAHP were mimicked by the beta-adrenergic agonist isoproterenol, but not by the alpha-adrenergic agonists clonidine or phenylephrine at higher concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

The ether-à-go-go-Related Gene K+ Current: Functions of a Strange Inward Rectifier

Physiology ◽  
1999 ◽  
Vol 14 (4) ◽  
pp. 135-142 ◽  
Author(s):  
Jürgen R. Schwarz ◽  
Christiane K. Bauer
Keyword(s):  
Prolactin Secretion ◽  
Inward Rectifier ◽  
Resting Potential ◽  
Related Gene ◽  
Cardiac Action ◽  
Signal Cascade ◽  
Action Potential Frequency ◽  
K Current ◽  
Intracellular Signal ◽  
Potential Frequency

The erg channels mediate an inward-rectifying K+ current because of their peculiar gating kinetics. They are involved in repolarization of the cardiac action potential, frequency adaptation, and maintenance of the resting potential. Reduction of erg currents via an intracellular signal cascade underlies the thyrotropin-releasing hormone-induced increase in prolactin secretion.

Changes in K+ currents induced by Ba2+ in guinea pig ventricular muscles

1986 ◽  
Vol 251 (1) ◽  
pp. H24-H33 ◽  
Author(s):  
Y. Hirano ◽  
M. Hiraoka
Keyword(s):  
Guinea Pig ◽  
Time Dependent ◽  
Resting Potential ◽  
Dependent Component ◽  
Voltage Dependent ◽  
K Current ◽  
Sucrose Gap ◽  
Time Courses ◽  
K Currents ◽  
Potential Level

Effects of Ba2+ on the K+ currents of guinea pig ventricular muscle were studied using the single sucrose-gap voltage-clamp technique. Ba2+ decreased the late (1- or 2-s) current at any potential level, with stronger suppression in the slope conductance at resting potential level than at depolarized voltages above 0 mV. During depolarizing pulses beyond -40 mV, Ba2+ reduced both the time-dependent and time-independent current components, indicating suppression of both outward and background K+ currents (IK and IK1, respectively), whereas tail currents after repolarization to -40 mV increased, with their time courses having double exponentials. These apparent conflicting results between IK and the tail current could not be explained by extracellular K+ fluctuation, because 20 mM Cs+ alone depressed both factors, but an additional application of Ba2+ caused an increase in both components compared with those in the former condition. On hyperpolarization below -60 mV, a time-dependent decrease in the inward current was observed after Ba2+ application without an activation of If. The decrease was stronger and faster at negative potential levels. These results are compatible with a time- and voltage-dependent blocking action of Ba2+ on the inward rectifier K+ current reported in other cardiac and noncardiac tissues. In two components of the tail currents after repolarization from depolarizing voltage steps during Ba2+ application, the faster one can probably be attributed to this blocking action of IK1, whereas the slower one can be attributed to the deactivation of IK. This time-dependent component of IK1 may contribute to the generation of Ba2+-induced automaticity at the depolarized state.

Reduction of voltage-activated K+ currents by forskolin is not mediated via cAMP in pleural sensory neurons of Aplysia

1990 ◽  
Vol 64 (5) ◽  
pp. 1474-1483 ◽  
Author(s):  
D. A. Baxter ◽  
J. H. Byrne
Keyword(s):  
Adenylate Cyclase ◽  
Sensory Neurons ◽  
Water Solubility ◽  
Membrane Current ◽  
Peak Amplitude ◽  
Bath Application ◽  
Voltage Dependent ◽  
K Current ◽  
Derivatives Of ◽  
K Currents

1. Forskolin is often used to activate adenylate cyclase in studies relating adenosine 3',5'-cyclic monophosphate (cAMP) to the modulation of membrane current. There is growing concern, however, that some actions of forskolin are independent of cAMP. With the use of two-electrode voltage-clamp techniques, we compared the effects of analogues of cAMP to the effects of forskolin on K+ currents in somata of sensory neurons that were isolated from pleural ganglia of Aplysia californica. 2. Analogues of cAMP did not reduce the peak amplitude of either the transient K+ current (IA) or the voltage-dependent K+ current (IK.V). Analogues of cAMP did reduce the previously described cAMP-sensitive S K+ current (IK.S). In contrast, forskolin reduced the peak amplitude of both IA and IK.V. Furthermore, both IA and IK.V were reduced by 1,9-dideoxy-forskolin, a derivative of forskolin that does not activate adenylate cyclase. These results indicate that the effects of forskolin and 1,9-dideoxy-forskolin on IA and IK.V were not mediated via cAMP. 3. Bath application of a modified form of forskolin (7-deacetyl-6-[N-acetylglycyl]-forskolin), which has enhanced water solubility and activates adenylate cyclase, reduced IK.S, but did not alter either IA or IK.V. Thus it appears that certain derivatives of forskolin can be used to activate adenylate cyclase and avoid some of the nonspecific actions on membrane current that are associated with forskolin.

Serotonergic modulation of two potassium currents in the pleural sensory neurons of Aplysia

1989 ◽  
Vol 62 (3) ◽  
pp. 665-679 ◽  
Author(s):  
D. A. Baxter ◽  
J. H. Byrne
Keyword(s):  
Membrane Potentials ◽  
Membrane Current ◽  
Membrane Currents ◽  
Independent Component ◽  
Multiple Components ◽  
Dependent Component ◽  
Voltage Dependent ◽  
K Current ◽  
Pleural Ganglion ◽  
K Currents

1. The properties of membrane currents that were modulated by serotonin (5-HT) were investigated with two-electrode voltage-clamp techniques in sensory neuron somata isolated from the pleural ganglion of Aplysia californica. The modulatory effects of 5-HT were revealed by computer subtraction of current responses elicited in the presence of 5-HT from current responses elicited prior to the application of 5-HT. The complexities of the resulting 5-HT difference currents (I5-HT) suggested that 5-HT modulated more than one component of membrane current. 2. The 5-HT difference currents appeared to have at least two distinct components. One component was clearly evident at membrane potentials more negative than -10 mV was relatively voltage independent and did not inactivate. A second component was activated at membrane potentials more positive than -10 mV, had complex kinetics, and was highly voltage dependent. In an attempt to identify the membrane currents that were modulated by 5-HT, we compared the pharmacologic sensitivity of I5-HT to that of previously described K+ currents. 3. The two components of I5-HT had different sensitivities to agents that block K+ currents. The relatively voltage-independent component of I5-HT was not blocked by 2 mM 4-aminopyridine (4-AP) and was relatively insensitive to tetraethylammonium (TEA) (estimated Kd of 92 mM). In contrast, the voltage-dependent component of I5-HT was blocked by 4-AP (2 mM) and moderate concentrations of TEA (estimated Kd of 5 mM). 4. The K+ current blockers that were used to examine I5-HT were also used to examine voltage-activated membrane currents. Externally applied TEA blocked the delayed or voltage-dependent K+ current (IK.V) with an estimated dissociation constant (Kd) of 8 mM and a membrane current similar to the Ca2+-activated K+ current (IK.Ca) with an estimated Kd of 0.4 mM. In addition, externally applied 4-AP (2 mM) blocked IK.V. Thus TEA and 4-AP were equipotent in blocking both IK.V and the voltage-dependent component of I5-HT. 5. The suggestion that I5-HT contained multiple components was supported further by examining the modulatory effects of adenosine 3',5'-cyclic monophosphate (cAMP) that mediates some actions of 5-HT on membrane currents in these cells. cAMP difference currents (IcAMP) were similar to the relatively voltage-independent component of I5-HT. The subsequent addition of 5-HT to solutions already containing cAMP resulted in 5-HT difference currents similar to the voltage-dependent component of I5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Voltage-dependent and odorant-regulated currents in isolated olfactory receptor neurons of the channel catfish.

1992 ◽  
Vol 99 (4) ◽  
pp. 505-529 ◽  
Author(s):  
T Miyamoto ◽  
D Restrepo ◽  
J H Teeter
Keyword(s):  
Action Potentials ◽  
Olfactory Receptor Neurons ◽  
Olfactory Neurons ◽  
Outward Currents ◽  
Na Currents ◽  
Voltage Dependent ◽  
Inward Currents ◽  
K Current ◽  
Receptor Neurons ◽  
K Currents

The electrical properties of olfactory receptor neurons, enzymatically dissociated from the channel catfish (Ictalurus punctatus), were studied using the whole-cell patch-clamp technique. Six voltage-dependent ionic currents were isolated. Transient inward currents (0.1-1.7 nA) were observed in response to depolarizing voltage steps from a holding potential of -80 mV in all neurons examined. They activated between -70 and -50 mV and were blocked by addition of 1 microM tetrodotoxin (TTX) to the bath or by replacing Na+ in the bath with N-methyl-D-glucamine and were classified as Na+ currents. Sustained inward currents, observed in most neurons examined when Na+ inward currents were blocked with TTX and outward currents were blocked by replacing K+ in the pipette solution with Cs+ and by addition of 10 mM Ba2+ to the bath, activated between -40 and -30 mV, reached a peak at 0 mV, and were blocked by 5 microM nimodipine. These currents were classified as L-type Ca2+ currents. Large, slowly activating outward currents that were blocked by simultaneous replacement of K+ in the pipette with Cs+ and addition of Ba2+ to the bath were observed in all olfactory neurons examined. The outward K+ currents activated over approximately the same range as the Na+ currents (-60 to -50 mV), but the Na+ currents were larger at the normal resting potential of the neurons (-45 +/- 11 mV, mean +/- SD, n = 52). Four different types of K+ currents could be differentiated: a Ca(2+)-activated K+ current, a transient K+ current, a delayed rectifier K+ current, and an inward rectifier K+ current. Spontaneous action potentials of varying amplitude were sometimes observed in the cell-attached recording configuration. Action potentials were not observed in whole-cell recordings with normal internal solution (K+ = 100 mM) in the pipette, but frequently appeared when K+ was reduced to 85 mM. These observations suggest that the membrane potential and action potential amplitude of catfish olfactory neurons are significantly affected by the activity of single channels due to the high input resistance (6.6 +/- 5.2 G omega, n = 20) and low membrane capacitance (2.1 +/- 1.1 pF, n = 46) of the cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Somatostatin increases voltage-dependent potassium currents in rat somatotrophs

1990 ◽  
Vol 259 (6) ◽  
pp. C854-C861 ◽  
Author(s):  
C. Chen ◽  
J. Zhang ◽  
J. D. Vincent ◽  
J. M. Israel
Keyword(s):  
Growth Hormone ◽  
Cell Voltage ◽  
Inhibitory Effect ◽  
Delayed Rectifier ◽  
Hormone Release ◽  
Growth Hormone Release ◽  
Voltage Dependent ◽  
Inward Currents ◽  
K Current ◽  
K Currents

To study the modulatory effects of somatostatin on membrane K+ currents, whole cell voltage-clamp recordings were performed on identified rat somatotrophs in primary culture. In the presence of Co2+ (2 mM) and tetrodotoxin (1 microM) in the bath solution to block Ca2+ and Na+ inward currents, two types of voltage-activated K+ currents were identified on the basis of their kinetics and pharmacology. First, a delayed rectifier K+ current (IK) had a threshold of -20 mV, did not decay during voltage steps lasting 300 ms, and was markedly attenuated by extracellular application of tetraethylammonium (TEA, 10 mM). Second, a transient outward K+ current (IA) was activated at -40 mV (from a holding potential of -80 mV) and persisted despite the presence of TEA. This IA was blocked by 4-aminopyridine (2 mM). Somatostatin (10 nM) increased IK by 75% and IA by 45% without obvious effects on steady-state voltage dependency of activation or inactivation, and these effects were reversible. This increase in K+ currents may contribute in part to the inhibitory effect of somatostatin on growth hormone release.

scholarly journals Novel K+-channel-blocking toxins from the venom of the scorpion Centruroides limpidus limpidus Karsch

1994 ◽  
Vol 304 (1) ◽  
pp. 51-56 ◽  
Author(s):  
B M Martin ◽  
A N Ramirez ◽  
G B Gurrola ◽  
M Nobile ◽  
G Prestipino ◽  
...  
Keyword(s):  
Primary Structure ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
K Channel ◽  
Amino Acid Residues ◽  
Channel Blocking ◽  
Voltage Dependent ◽  
K Current ◽  
Current Reduction ◽  
K Currents

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.

scholarly journals Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt KV4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties

2021 ◽  
Vol 22 (9) ◽  
pp. 4986
Author(s):  
Ginevra Zanni ◽  
Chen-Tsung Hsiao ◽  
Ssu-Ju Fu ◽  
Chih-Yung Tang ◽  
Alessandro Capuano ◽  
...  
Keyword(s):  
Calcium Influx ◽  
Cerebellar Atrophy ◽  
Loss Of Function ◽  
Protein Levels ◽  
Expression Studies ◽  
Targeted Ngs ◽  
Voltage Dependent ◽  
K Current ◽  
Channel Properties ◽  
K Currents

KCND3 encodes the voltage-gated potassium channel KV4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function KV4.3 mutations have been associated with dominant spinocerebellar ataxia (SCA19/22). By targeted NGS sequencing, we identified two novel KCND3 missense variants of the KV4.3 channel: p.S347W identified in a patient with adult-onset pure cerebellar syndrome and p.W359G detected in a child with congenital nonprogressive ataxia. Neuroimaging showed mild cerebellar atrophy in both patients. We performed a two-electrode voltage-clamp recording of KV4.3 currents in Xenopus oocytes: both the p.G345V (previously reported in a SCA19/22 family) and p.S347W mutants exhibited reduced peak currents by 50%, while no K+ current was detectable for the p.W359G mutant. We assessed the effect of the mutations on channel gating by measuring steady-state voltage-dependent activation and inactivation properties: no significant alterations were detected in p.G345V and p.S347W disease-associated variants, compared to controls. KV4.3 expression studies in HEK293T cells showed 53% (p.G345V), 45% (p.S347W) and 75% (p.W359G) reductions in mutant protein levels compared with the wildtype. The present study broadens the spectrum of the known phenotypes and identifies additional variants for KCND3-related disorders, outlining the importance of SCA gene screening in early-onset and congenital ataxia.

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