High Conductance Calcium-Activated Potassium Channels

Kaczorowski, Gregory J.; Jones, Thomas R.

doi:10.1007/978-3-0348-7362-8_8

Cited by 25 publications

(25 citation statements)

References 99 publications

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“…A similar increase in the opening of BK Ca channels was seen in ventromedial hippocampal neurones (23). In all cases the effect of NS1619 was inhibited by iberiotoxin, a highly potent and selective blocker of BK Ca channels (16,33,34). However, NS1619 also blocked voltage operated calcium channels and K DR channels, and NS1619-evoked relaxation of both the basilar artery and portal vein was concluded to be due to a direct inhibition of calcium currents, rather than via BK Ca channel mediated cellular hyperpolarisation, since the relaxation was not fully prevented by iberiotoxin or charybdotoxin.…”

Section: Discussionsupporting

confidence: 63%

“…However, BK Ca channels, as well as other potassium channels such as ATPdependent (K ATP ) and voltage-dependent delayed rectifier (K DR ) potassium channels have also been shown to be present on airway smooth muscle from a number of species (16,28). BK Ca channels may be important regulators of the membrane potential and intrinsic tone of human and guinea pig airway smooth muscle (29,30).…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis was based on the use of charybdotoxin, a relatively nonselective blocker of BK Ca channels, and its ability to reverse the inhibitory action of these receptors. Such studies are necessarily complicated by the presence of several types of potassium channel, including BK Ca channels, on airway smooth muscle (16), and the existence of these channels on airway nerves has not yet been demonstrated directly. Moreover, it is not known if the afferent activity of sensory fibers, and in particular that of myelinated RARs, is similarly modulated, and if this may be reflected in a corresponding inhibition of a central reflex pathway.…”

Section: Introductionmentioning

confidence: 99%

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Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the guinea pig.

Fox¹,

Barnes²,

Venkatesan³

et al. 1997

J. Clin. Invest.

101

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Sensory nerves play an important role in airway disease by mediating central reflexes such as cough, and local axon reflexes resulting in the peripheral release of neuropeptides. We have tested whether the benzimidazolone compound, NS1619, an opener of large conductance calcium-activated potassium (BK Ca ) channels, inhibits the activity of sensory fibers, and central and local airway reflexes in guinea pig airways. In in vitro single fiber recording experiments, NS1619 applied to identified receptive fields in the trachea inhibited the firing of A ␦ -fibers evoked by hypertonic saline and distilled water, and bradykinin-evoked firing of C-fibers. Electrically evoked nonadrenergic noncholinergic contractions of isolated bronchi mediated by the release of neurokinin A (NKA) from C-fibers, but not those elicited by exogenous NKA, were inhibited by NS1619. These effects of NS1619 were prevented by iberiotoxin, a selective blocker of BK Ca channels. In conscious guinea pigs, cough evoked by aerosolized citric acid was also inhibited by NS1619. These data show that BK Ca channel activation inhibits sensory nerve activity, resulting in a reduction of both afferent and efferent function. BK Ca channel openers may therefore be of potential benefit in reducing neurogenic inflammation and central reflexes seen during inflammatory conditions of the airways, and may represent a new class of antitussive drug. ( J. Clin. Invest. 1997. 99:513-519.)

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the guinea pig.

Fox¹,

Barnes²,

Venkatesan³

et al. 1997

J. Clin. Invest.

101

View full text Add to dashboard Cite

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“…BK channels likely share similar pore structural determinants and sensitivities to toxins with voltage-dependent K + channels (K V channels) [4] . Some peptidyl scorpion toxins such as Charybdotoxin (ChTX) not only block K V 1.3 as well as a mutation F425H of shaker channels, but also block the BK currents encoded by both the Slo1 a subunits and the b subunits but with a higher EC 50 [3,11,12] . In Figure 1, a conserved residue Phe266 (mSlo1) labeled with the symbol ▼ (the upper panel) is supposed to interact with the residues that are highlighted in the lower panel with the same symbol [4,13] .…”

Section: +mentioning

confidence: 99%

Residue Phe266 in S5-S6 loop is not critical for Charybdotoxin binding to Ca2+-activated K+ (mSlo1) channels1

Yao

Gan

et al. 2006

Acta Pharmacologica Sinica

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Aim: To gain insight into the interaction between the Charybdotoxin (ChTX) and BK channels. Methods: Site-directed mutagenesis was used to make two mutants: mSlo1-F266L and mSlo1-F266A. The two mutants were then expressed in Xenopus oocytes and their effects were tested on ChTX by electrophysiology experiments. Results: We demonstrate an equilibrium dissociation constant K d = 3.1-4.2 nmol/L for both the mutants mSlo1-F266L and mSlo1-F266A similar to that of the wild-type mSlo1 K d =3.9 nmol/L. Conclusion: The residue Phe266 does not play a crucial role in binding to ChTX, which is opposed to the result arising from the simulation of peptide-channel interaction.

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“…In recent years, Ahern et al (59) have demonstrated that NO activates large conductance Ca 2+ -activated K + channels (also called BK or Maxi-K channels) of the axon terminals in the posterior pituitary, by a cGMP-independent mechanism. In neurons, BK channels participates in repolarization and fast afterhyperpolarization of action potential, affecting the amount of neurotransmitter release (60) and, therefore, the excitability of neurons. Activation of BK channels by NO in the terminals of magnocellular neurons in the posterior pituitary depresses the excitability of the terminals.…”

Section: No and Signal-transduction Pathwaymentioning

confidence: 99%

Nitric oxide modulation of the hypothalamo-neurohypophyseal system

Kadekaro

2004

Braz J Med Biol Res

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Nitric oxide (NO), a free radical gas produced endogenously from the amino acid L-arginine by NO synthase (NOS), has important functions in modulating vasopressin and oxytocin secretion from the hypothalamo-neurohypophyseal system. NO production is stimulated during increased functional activity of magnocellular neurons, in parallel with plastic changes of the supraoptic nucleus (SON) and paraventricular nucleus. Electrophysiological data recorded from the SON of hypothalamic slices indicate that NO inhibits firing of phasic and non-phasic neurons, while L-NAME, an NOS inhibitor, increases their activity. Results from measurement of neurohypophyseal hormones are more variable. Overall, however, it appears that NO, tonically produced in the forebrain, inhibits vasopressin and oxytocin secretion during normovolemic, isosmotic conditions. During osmotic stimulation, dehydration, hypovolemia and hemorrhage, as well as high plasma levels of angiotensin II, NO inhibition of vasopressin neurons is removed, while that of oxytocin neurons is enhanced. This produces a preferential release of vasopressin over oxytocin important for correction of fluid imbalance. During late pregnancy and throughout lactation, fluid homeostasis is altered and expression of NOS in the SON is down-and up-regulated, respectively, in parallel with plastic changes of the magnocellular system. NO inhibition of magnocellular neurons involves GABA and prostaglandin synthesis and the signal-transduction mechanism is independent of the cGMP-pathway. Plasma hormone levels are unaffected by icv 1H-[1, 2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor) or 8-Br-cGMP administered to conscious rats. Moreover, cGMP does not increase in homogenates of the neural lobe and in microdialysates of the SON when NO synthesis is enhanced during osmotic stimulation. Among alternative signal-transduction pathways, nitrosylation of target proteins affecting activity of ion channels is considered.

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High Conductance Calcium-Activated Potassium Channels

Cited by 25 publications

References 99 publications

Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the guinea pig.

Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the guinea pig.

Residue Phe266 in S5-S6 loop is not critical for Charybdotoxin binding to Ca2+-activated K+ (mSlo1) channels1

Nitric oxide modulation of the hypothalamo-neurohypophyseal system

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