K+ channels involved in contractility of rabbit small intestine

Lamarca, Violeta; Grasa, Laura; Fagundes, Diego Santos; Arruebo, M. P.; Plaza, Miguel Ángel; Murillo, María Divina

doi:10.1007/bf03165751

Cited by 11 publications

(11 citation statements)

References 28 publications

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“…The E-4031-induced concentration-dependent increase in epididymal SC amplitude may reflect an increase in action potentials per "slow wave." E-4031 also increased the amplitude of spontaneous contractions in the guinea pig urinary bladder (14) and the rabbit small intestine (18), whereas in the human jejunum, high concentrations of the compound (1 M) replaced phasic contractions with small tonic contractures due to the elimination of slow waves (8). The mechanism of the E-4031-evoked reduction in epididymal SC frequency is unknown, but the phenomenon equals the findings in the portal vein.…”

Section: Discussionmentioning

confidence: 84%

“…E-4031-sensitive currents have also been detected in SMC of the esophagus (1), portal vein (28), gallbladder (29), stomach (27) and intestine (8,18,20). It is assumed that, in SMC, erg currents serve the function of threshold currents; a pharmacological block of erg channels depolarizes the membrane potential, which is correlated with muscle contraction (see Ref.…”

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confidence: 98%

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Erg K⁺ channels modulate contractile activity in the bovine epididymal duct

Mewe¹,

Wulfsen²,

Schuster³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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The expression and functional role of ether-à-go-go-related gene (erg) K+ channels were examined in the bovine epididymal duct. Sperm transit through the epididymal duct relies on spontaneous phasic contractions (SC) of the peritubular smooth muscle wall. Isometric tension studies revealed SC-enhancing effects of the erg channel blockers E-4031, dofetilide, cisapride, and haloperidol and SC-suppressing effects of the activator NS-1643. In the corpus epididymidis, EC50 values of 32 nM and 8.3 microM were determined for E-4031 and NS-1643, respectively. E-4031 was also able to elicit contraction in epithelium-denuded corpus segments, which lacked SC. In the cauda region, E-4031 and NS-1643 exerted effects on agonist-induced contraction similar to those observed in the proximal duct. Experiments with nifedipine and thapsigargin suggested that the excitatory effects of E-4031 depended mainly on external calcium influx and not on intracellular calcium release. Western blot and RT-PCR assays revealed the expression of both, erg1a and erg1b, in all duct regions. Because erg1b appears to predominate in the epididymal duct, patch-clamp experiments were performed on heterologously expressed erg1b channels to investigate the sensitivity of this splice variant to NS-1643. In contrast to its effects on erg1a, NS-1643 induced a concentration-dependent current increase mainly due to a marked leftward shift in erg1b channel activation by approximately 30 mV at 10 microM, explaining the inhibitory effect of the drug on epididymal SC. In summary, these data provide strong evidence for a physiological role of erg1 channels in regulating epididymal motility patterns.

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Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 98%

Erg K⁺ channels modulate contractile activity in the bovine epididymal duct

Mewe¹,

Wulfsen²,

Schuster³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…2). EAG/ERG/ELK (Kv10, 11 and 12) subfamilies were excluded from the present study as addition of E4031 (1 μ m ) to the internal patch solution and left the current unaffected (Gessner & Heinemann, 2003; Royer et al 2005; Lamarca et al 2006; Furlan et al 2007). Contributions from HCN channels were routinely blocked by inclusion of ZD 7288 (10 μ m ) in the patch solution.…”

Section: Resultsmentioning

confidence: 99%

Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons

Johnston

Griffin

Baker

et al. 2008

The Journal of Physiology

113

163

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The medial nucleus of the trapezoid body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K + current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of ∼37 nS; it is half-activated at −9.2 ± 2.1 mV and half-inactivated at −35.9 ± 1.5 mV. It is blocked by several non-specific potassium channel antagonists including quinine (100 μm) and high concentrations of extracellular tetraethylammonium (TEA; IC 50 = 11.8 mm), but no specific antagonists were found. These characteristics are similar to recombinant Kv2-mediated currents. Quantitative RT-PCR showed that Kv2.2 mRNA was much more prevalent than Kv2.1 in the MNTB. A Kv2.2 antibody showed specific staining and Western blots confirmed that it recognized a protein ∼110 kDa which was absent in brainstem tissue from a Kv2.2 knockout mouse. Confocal imaging showed that Kv2.2 was highly expressed in axon initial segments of MNTB neurons. In the absence of a specific antagonist, Hodgkin-Huxley modelling of voltage-gated conductances showed that Kv2.2 has a minor role during single APs (due to its slow activation) but assists recovery of voltage-gated sodium channels (Nav) from inactivation by hyperpolarizing interspike potentials during repetitive AP firing. Current-clamp recordings during high frequency firing and characterization of Nav inactivation confirmed this hypothesis. We conclude that Kv2.2-containing channels have a distinctive initial segment location and crucial function in maintaining AP amplitude by regulating the interspike potential during high frequency firing. Potassium currents have multiple and diverse roles in shaping electrical signalling, with different suites of voltage-gated and rectifying non-gated channels setting neuronal membrane potentials, firing threshold, action potential waveform and firing patterns. Identification of the channel family and subunits contributing to these functions in native neurons is complicated by their heterogeneous subunit composition, their particular functional localization to the plasma membrane and by the absence of specific antagonists for some families. For these reasons the full complement of the K + channels and subunits underlying native K + currents are still not known for any identified central neuron. We have focused on studying the potassium currents of a 'simple' neuron This paper has online supplemental material.within the medial nucleus of the trapezoid body (MNTB), which serves as a relay in the binaural circuits involved in sound source localization. These neurons receive the glutamatergic calyx of Held giant synapse, which reliably triggers postsynaptic APs with large, well-timed EPSCs which have a magnitude of around 30 times firing threshold. In vivo recordings show the calyceal input fires spontaneously at frequencies ranging between 0 and 100 Hz ...

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“…mediate ACh-and KCl-induced contractions [23] , and K + channels mediate spontaneous contractions in rabbit intestine [38] .…”

Section: +mentioning

confidence: 99%

Contractile effect of tachykinins on rabbit small intestine

et al. 2011

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Aim: To study the role of the tachykinin receptors in spontaneous contractions of longitudinal and circular smooth muscle from rabbit small intestine and to determine the mechanism of action of Substance P (SP). Methods: Rabbit duodenum, jejunum and ileum segments were prepared. The spontaneous contractions of longitudinal and circular smooth muscle were recorded using a computer via an isometric force transducer. The specific agonists and antagonists of tachykinin receptors were added into the organ bath. Results: The agonists of tachykinin NK1 receptor (SP and [Sar9] SP), NK2 receptor (NKA and (β-Ala8)-NKA), and NK3 receptor (NKB and Senktide) all induced contractions in the small intestine. The contractions were diminished by NK1 receptor antagonist L-733,060, NK2 receptor antagonist GR-94800, and NK3 receptor antagonist SB 218795. Contractions caused by SP were also reduced by atropine, verapamil, PKC inhibitor staurosporine, and PLC inhibitor U73122. Conclusion: Ttachykinin NK1, NK2, and NK3 receptors mediate the contractions of the smooth muscle in rabbit intestine. Furthermore, SP acts directly on smooth muscle cells through the tachykinin NK1 receptor.

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K+ channels involved in contractility of rabbit small intestine

Cited by 11 publications

References 28 publications

Erg K⁺ channels modulate contractile activity in the bovine epididymal duct

Erg K⁺ channels modulate contractile activity in the bovine epididymal duct

Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons

Contractile effect of tachykinins on rabbit small intestine

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K+ channels involved in contractility of rabbit small intestine

Cited by 11 publications

References 28 publications

Erg K+ channels modulate contractile activity in the bovine epididymal duct

Erg K+ channels modulate contractile activity in the bovine epididymal duct

Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons

Contractile effect of tachykinins on rabbit small intestine

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Erg K⁺ channels modulate contractile activity in the bovine epididymal duct

Erg K⁺ channels modulate contractile activity in the bovine epididymal duct